EP3728253B1 - 6-azaindole compounds - Google Patents

Description

• The present invention generally relates to 6-azaindole compounds useful as inhibitors of signaling through Toll-like receptor 7, 8, or 9 (TLR7, TLR8, TLR9) or combinations thereof. Provided herein are 6-azaindole compounds, compositions comprising such compounds, and uses thereof. The invention further pertains to pharmaceutical compositions containing at least one compound according to the invention that are useful for the treatment of conditions related to TLR modulation, such as inflammatory and autoimmune diseases, and for inhibiting the activity of TLRs in a mammal.
• Toll/IL-1 receptor family members are important regulators of inflammation and host resistance. The Toll-like receptor family recognizes molecular patterns derived from infectious organisms including bacteria, fungi, parasites, and viruses (reviewed in Kawai, T. et al., Nature Immunol., 11:373-384 (2010)). Ligand binding to the receptor induces dimerization and recruitment of adaptor molecules to a conserved cytoplasmic motif in the receptor termed the Toll/IL-1 receptor (TIR) domain with the exception of TLR3, all TLRs recruit the adaptor molecule MyD88. The IL-1 receptor family also contains a cytoplasmic TIR motif and recruits MyD88 upon ligand binding (reviewed in Sims, J.E. et al., Nature Rev. Immunol., 10:89-102 (2010)).
• Toll-like receptors (TLRs) are a family of evolutionarily conserved, transmembrane innate immune receptors that participate in the first-line defense. As pattern recognition receptors, the TLRs protect against foreign molecules, activated by pathogen associated molecular patterns (PAMPs), or from damaged tissue, activated by danger associated molecular patterns (DAMPs). A total of 13 TLR family members have been identified, 10 in human, that span either the cell surface or the endosomal compartment. TLR7/8/9 are among the set that are endosomally located and respond to single-stranded RNA (TLR7 and TLR8) or unmethylated single-stranded DNA containing cytosine-phosphate-guanine (CpG) motifs (TLR9).
• Activation of TLR7/8/9 can initiate a variety of inflammatory responses (cytokine production, B cell activation and IgG production, Type I interferon response). In the case of autoimmune disorders, the aberrant sustained activation of TLR7/8/9 leads to worsening of disease states. Whereas overexpression of TLR7 in mice has been shown to exacerbate autoimmune disease, knockout of TLR7 in mice was found to be protective against disease in lupus-prone MRL/lpr mice. Dual knockout of TLR7 and 9 showed further enhanced protection.
• As numerous conditions may benefit by treatment involving modulation of cytokines, IFN production and B cell activity, it is immediately apparent that new compounds capable of modulating TLR7 and/or TLR8 and/or TLR9 and could provide substantial therapeutic benefits to a wide variety of patients.
• Document WO 2006/113458 discloses heterocyclic inhibitors of protein arginine methyl transferases.
• The present invention relates to a new class of 6-azaindole compounds found to be effective inhibitors of signaling through TLR7/8/9. These compounds are provided to be useful as pharmaceuticals with desirable stability, bioavailability, therapeutic index, and toxicity values that are important to their drugability.
SUMMARY OF THE INVENTION
• The present invention provides compounds of Formula (I) that are useful as inhibitors of signaling through Toll-like receptor 7, 8, or 9 and are useful for the treatment of proliferative diseases, allergic diseases, autoimmune diseases and inflammatory diseases, or stereoisomers, N-oxides, tautomers, pharmaceutically acceptable salts, or solvates thereof.
• The present invention also provides pharmaceutical compositions comprising a pharmaceutically acceptable carrier and at least one of the compounds of the present invention or stereoisomers, tautomers, pharmaceutically acceptable salts, or solvates thereof.
• The present invention also provides at least one of the compounds of the present invention or stereoisomers, tautomers, pharmaceutically acceptable salts, or solvates thereof for use in the inhibition of Toll-like receptor 7, 8, or 9 in a host in need of such treatment.
• The present invention also provides at least one of the compounds of the present invention or stereoisomers, tautomers, pharmaceutically acceptable salts, or solvates thereof for use in treating proliferative, metabolic, allergic, autoimmune and inflammatory diseases, in a host in need of such treatment.
• The present invention also provides at least one of the compounds of Formula (I) or salts, and solvates thereof for use in treating a disease or disorder associated with Toll-like receptor 7, 8, or 9 activity, in a mammal in need thereof.
• The present invention also provides processes and intermediates for making the compounds of Formula (I) including salts, and solvates thereof.
• The present invention also provides at least one of the compounds of Formula (I) or salts, and solvates thereof, for use in therapy.
• The compound of Formula (I) and compositions comprising the compounds of Formula (I) may be used in treating, preventing, or curing various Toll-like receptor 7, 8, or 9 related conditions. Pharmaceutical compositions comprising these compounds are useful for treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as allergic disease, autoimmune diseases, inflammatory diseases, and proliferative diseases.
• These and other features of the invention will be set forth in expanded form as the disclosure continues.
DETAILED DESCRIPTION
• The first aspect of the present invention provides at least one compound of Formula (I):

  

  N-oxide, stereoisomers, tautomers, solvates or a pharmaceutically-acceptable salt thereof, wherein:
  G is:

  

  A is:
1. (i) -NR₇R₈ wherein R₇ and R₈ together with the nitrogen atom to which they are attached form a heterocyclic ring selected from piperazinyl, piperidinyl, or diazaspiro[3.3]heptanyl, wherein said heterocyclic ring is substituted with zero to 1 R_7b and zero to 1 R_7c; or
2. (ii) -CHR₁₂R₁₃, wherein R₁₂ and R₁₃ together with the carbon atom to which they are attached form a cyclic group selected from cyclopentyl, cyclohexyl, morpholinyl, or piperidinyl, each substituted with zero to 1 R_12a;
• R₁ is -CH(CH₃)₂;
• each R₂ is independently -CH₃ or -OCH₃;
• each R₅ is independently F, Cl, or -CH₃;
• R_7b is:
  1. (i) -CH₃, -CH₂CH₃, -CH₂CH₂CH₃, -CH(CH₃)₂, -CH₂CH(CH₃)₂, -CH₂CF₃, -CH₂CN, -CH₂C(CH₃)₂OH, -CH₂CH₂OCH₃, -CH₂CH₂S(O)₂CH₃, -(CH₂)_1-2NR_xR_x, -CH₂C(O)NR_xR_x, -NR_xR_y, -NR_x(C_1-4 hydroxyalkyl), -NH(CH₂CR_xR_xOCH₃), -NR_y(C_1-2 cyanoalkyl), -NR_x(C_1-2 fluoroalkyl), -NR_x(C_2-5 hydroxyfluoroalkyl), -NR_x(CH₂)_1-2C(O)NR_xR_x, -NR_x(CH₂)_1-3NR_xR_x, -NR_xCH₂CH₂N(CH₃)₂, -NR_xC(O)(CH₂)_1-2NR_xR_x, -C(O)CH₃, -C(O)CH₂NR_xR_x, -S(O)₂CH₃, -(CH₂)_1-2R_7d, -CH₂C(O)R_7d, -C(O)CH₂R_7d, -NHR_7d, -NH(CH₂)_1-2R_7d, or -OR_7d; or
  2. (ii) azetidinyl, cyclobutyl, dioxothiomorpholinyl, morpholinyl, oxaazaspiro[3.3]heptanyl, oxetanyl, piperazinonyl, piperazinyl, piperidinyl, tetrahydrofuranyl, or tetrahydropyranyl, each substituted with zero to 1 R_8a;
• each R_7c is -CH₃;
• R_7d is azaspiro[3.5]nonanyl, bicyclo[1.1.1]pentanyl, C_3-6 cycloalkyl, morpholinyl, oxetanyl, phenyl, piperidinyl, pyrazolyl, pyrrolidinyl, tetrahydrofuranyl, or tetrahydropyranyl, each substituted with zero to 1 substituent selected from C_1-3 alkyl, -NR_xR_x, -C(O)CH₃, methylpiperidinyl, methylpyrrolidinyl, tetramethylpiperidinyl, -OCH₂CH₂(pyrrolidinyl), and -OCH₂CH₂NHCH₂CH₃; and zero to 4 substituents selected from -CH₃;
• R_8a is -CH₃, -CH(CH₃)₂, or -S(O)₂CH₃;
• each R_12a is -CH(CH₃)₂, -CH₂CF₃, -CH₂C(CH₃)₂OH, -CH₂CH₂OCH₃, -CH₂C(O)NH(CH₃), -CH₂C(O)N(CH₃)₂, -CH₂C(O)NH₂, -CH₂CH₂S(O)₂CH₃, -CH₂CH₂NH(CH₃), -NR_xR_y, -NR_x(C_2-4 fluoroalkyl), -NH(CH₂C(CH₃)₂OH), -NH(CH₂CHFC(CH₃)₂OH), -NH(CH₂CH₂OCH₃), -NH(CH₂C(CH₃)₂OCH₃), -NR_x(CH₂C(O)NR_xR_x), -C(O)CH₂NH(CH₃), -C(O)CH₂N(CH₃)₂, R_12b, -CH₂R_12b, -NR_xR_12b, -N(CH2CN)Ri2b, or -NR_xCH₂R_12b;
• R_12b is azetidinyl, bicyclo[1.1.1]pentanyl, oxaazaspiro[3.3]heptanyl, oxetanyl, piperidinyl, tetrahydrofuranyl, or tetrahydropyranyl, each substituted with zero to 4 substituents independently selected from -CH₃, -CH(CH₃)₂, -CH₂OH, or -OCH₃; each R_x is independently H or -CH₃;
• n is zero or 1; and
• p is zero, 1, 2, 3, or 4.
• One embodiment provides a compound of Formula (I), N-oxide, stereoisomers, tautomers, solvates or a pharmaceutically-acceptable salt thereof wherein G is:

  

  and A, R₁, R₅, and n are defined in the first aspect.
• One embodiment provides a compound of Formula (I), N-oxide, stereoisomers, tautomers, solvates or a pharmaceutically-acceptable alt thereof, wherein R₁ is -CH(CH₃)₂.
• One embodiment provides a compound of Formula (I), N-oxide, stereoisomers, tautomers, solvates or a pharmaceutically-acceptable salt thereof wherein A is:
1. (i) -NR₇R₈ wherein R₇ and R₈ together with the nitrogen atom to which they are attached form a heterocyclic ring selected from piperazinyl, piperidinyl, or diazaspiro[3.3]heptanyl, wherein said heterocyclic ring is substituted with zero to 1 R_7b and zero to 1 R_7c; or
2. (ii) -CHR₁₂R₁₃, wherein R₁₂ and R₁₃ together with the carbon atom to which they are attached form a cyclic group selected from cyclopentyl, cyclohexyl, morpholinyl, or piperidinyl, each substituted with zero to 1 R_12a;
and G, R₁, R₅, R_7b, R_7c, R_12a, and n are defined in the first aspect. Also included in this embodiment are compounds in which R₁ -CH(CH₃)₂; each R₂ is independently-CH₃ or -OCH₃; and p is zero, 1, or 2.
• One embodiment provides a compound of Formula (I), N-oxide, stereoisomers, tautomers, solvates or a pharmaceutically-acceptable salt thereof wherein said compound is selected from Examples 1 to 472.
• One embodiment provides a compound of Formula (I), N-oxide, stereoisomers, tautomers, solvates or a pharmaceutically-acceptable salt thereof wherein said compound is selected from Examples 1 to 351.
• One embodiment provides a compound of Formula (I), N-oxide, stereoisomers, tautomers, solvates or a pharmaceutically-acceptable salt thereof wherein said compound is selected from Examples 352 to 472.
• The present invention may be embodied in other specific forms. The invention encompasses all combinations of the aspects and/or embodiments of the invention noted herein. It is understood that any and all embodiments of the present invention may be taken in conjunction with any other embodiment or embodiments to describe additional embodiments. It is also to be understood that each individual element of the embodiments is meant to be combined with any and all other elements from any embodiment to describe an additional embodiment.
DEFINITIONS
• The features and advantages of the invention may be more readily understood by those of ordinary skill in the art upon reading the following detailed description. It is to be appreciated that certain features of the invention that are, for clarity reasons, described above and below in the context of separate embodiments, may also be combined to form a single embodiment. Conversely, various features of the invention that are, for brevity reasons, described in the context of a single embodiment, may also be combined so as to form sub-combinations thereof. Embodiments identified herein as exemplary or preferred are intended to be illustrative and not limiting.
• Unless specifically stated otherwise herein, references made in the singular may also include the plural. For example, "a" and "an" may refer to either one, or one or more.
• As used herein, the phrase "compounds" refers to at least one compound. For example, a compound of Formula (I) includes a compound of Formula (I) and two or more compounds of Formula (I).
• Unless otherwise indicated, any heteroatom with unsatisfied valences is assumed to have hydrogen atoms sufficient to satisfy the valences.
• The definitions set forth herein take precedence over definitions set forth in any patent, patent application, and/or patent application publication.
• Listed below are definitions of various terms used to describe the present invention. These definitions apply to the terms as they are used throughout the specification (unless they are otherwise limited in specific instances) either individually or as part of a larger group.
• Throughout the specification, groups and substituents thereof may be chosen by one skilled in the field to provide stable moieties and compounds.
• In accordance with a convention used in the art,

  

  is used in structural formulas herein to depict the bond that is the point of attachment of the moiety or substituent to the core or backbone structure.
• The terms "halo" and "halogen," as used herein, refer to F, Cl, Br, and I.
• The term "cyano" refers to the group -CN.
• The term "amino" refers to the group -NH₂.
• The term "oxo" refers to the group =O.
• The term "alkyl" as used herein, refers to both branched and straight-chain saturated aliphatic hydrocarbon groups containing, for example, from 1 to 12 carbon atoms, from 1 to 6 carbon atoms, and from 1 to 4 carbon atoms. Examples of alkyl groups include, but are not limited to, methyl (Me), ethyl (Et), propyl (e.g., n-propyl and i-propyl), butyl (e.g., n-butyl, i-butyl, sec-butyl, and t-butyl), and pentyl (e.g., n-pentyl, isopentyl, neopentyl), n-hexyl, 2-methylpentyl, 2-ethylbutyl, 3-methylpentyl, and 4-methylpentyl. When numbers appear in a subscript after the symbol "C", the subscript defines with more specificity the number of carbon atoms that a particular group may contain. For example, "C_1-6 alkyl" denotes straight and branched chain alkyl groups with one to six carbon atoms.
• The term "fluoroalkyl" as used herein is intended to include both branched and straight-chain saturated aliphatic hydrocarbon groups substituted with one or more fluorine atoms. For example, "C_1-4 fluoroalkyl" is intended to include C₁ C₂, C₃, and C₄ alkyl groups substituted with one or more fluorine atoms. Representative examples of fluoroalkyl groups include, but are not limited to, -CF₃ and -CH₂CF₃.
• The term "cyanoalkyl" includes both branched and straight-chain saturated alkyl groups substituted with one or more cyano groups. For example, "cyanoalkyl" includes -CH₂CN, -CH₂CH₂CN, and C_1-4 cyanoalkyl.
• The term "aminoalkyl" includes both branched and straight-chain saturated alkyl groups substituted with one or more amine groups. For example, "aminoalkyl" includes -CH₂NH₂, -CH₂CH₂NH₂, and C_1-4 aminoalkyl.
• The term "hydroxyalkyl" includes both branched and straight-chain saturated alkyl groups substituted with one or more hydroxyl groups. For example, "hydroxyalkyl" includes -CH₂OH, -CH₂CH₂OH, and C_1-4 hydroxyalkyl.
• The term "hydroxy-fluoroalkyl" includes both branched and straight-chain saturated alkyl groups substituted with one or more hydroxyl groups and one or more fluorine atoms. For example, "hydroxy-fluoroalkyl" includes -CHFCH₂OH, -CH₂CHFC(CH₃)₂OH, and C_1-4 hydroxy-fluoroalkyl.
• The term "cycloalkyl," as used herein, refers to a group derived from a nonaromatic monocyclic or polycyclic hydrocarbon molecule by removal of one hydrogen atom from a saturated ring carbon atom. Representative examples of cycloalkyl groups include, but are not limited to, cyclopropyl, cyclopentyl, and cyclohexyl. When numbers appear in a subscript after the symbol "C", the subscript defines with more specificity the number of carbon atoms that a particular cycloalkyl group may contain. For example, "C₃-C₆ cycloalkyl" denotes cycloalkyl groups with three to six carbon atoms.
• The term "alkoxy," as used herein, refers to an alkyl group attached to the parent molecular moiety through an oxygen atom, for example, methoxy group (-OCH₃). For example, "C_1-3 alkoxy" denotes alkoxy groups with one to three carbon atoms.
• The term "alkoxyalkyl," as used herein, refers to an alkoxy group attached through its oxygen atom to an alkyl group, which is attached to the parent molecular moiety, for example, methoxymethyl group (-CH₂OCH₃). For example, "C_2-4 alkoxyalkyl" denotes alkoxyalkyl groups with two to four carbon atoms, such as -CH₂OCH₃, -CH₂CH₂OCH₃, -CH₂OCH₂CH₃, and -CH₂CH₂OCH₂CH₃.
• The phrase "pharmaceutically acceptable" is employed herein to refer to those compounds, materials, compositions, and/or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit/risk ratio.
• The compounds of Formula (I) can be provided as amorphous solids or crystalline solids. Lyophilization can be employed to provide the compounds of Formula (I) as amorphous solids.
• It should further be understood that solvates (e.g., hydrates) of the compounds of Formula (I) are also within the scope of the present invention. The term "solvate" means a physical association of a compound of Formula (I) with one or more solvent molecules, whether organic or inorganic. This physical association includes hydrogen bonding. In certain instances the solvate will be capable of isolation, for example when one or more solvent molecules are incorporated in the crystal lattice of the crystalline solid. "Solvate" encompasses both solution-phase and isolable solvates. Exemplary solvates include hydrates, ethanolates, methanolates, isopropanolates, acetonitrile solvates, and ethyl acetate solvates. Methods of solvation are known in the art.
• Various forms of prodrugs are well known in the art and are described in:
1. a) The Practice of Medicinal Chemistry, Camille G. Wermuth et al., Ch 31, (Academic Press, 1996);
2. b) Design of Prodrugs, edited by H. Bundgaard, (Elsevier, 1985);
3. c) A Textbook of Drug Design and Development, P. Krogsgaard-Larson and H. Bundgaard, eds. Ch 5, pgs 113 - 191 (Harwood Academic Publishers, 1991); and
4. d) Hydrolysis in Drug and Prodrug Metabolism, Bernard Testa and Joachim M. Mayer, (Wiley-VCH, 2003).
• In addition, compounds of Formula (I), subsequent to their preparation, can be isolated and purified to obtain a composition containing an amount by weight equal to or greater than 99% of a compound of Formula (I) ("substantially pure"), which is then used or formulated as described herein. Such "substantially pure" compounds of Formula (I) are also contemplated herein as part of the present invention.
• "Stable compound" and "stable structure" are meant to indicate a compound that is sufficiently robust to survive isolation to a useful degree of purity from a reaction mixture, and formulation into an efficacious therapeutic agent. The present invention is intended to embody stable compounds.
• "Therapeutically effective amount" is intended to include an amount of a compound of the present invention alone or an amount of the combination of compounds claimed or an amount of a compound of the present invention in combination with other active ingredients effective to act as an inhibitor to TLR7/8/9, or effective to treat or prevent autoimmune and/or inflammatory disease states, such as SLE, IBD, multiple sclerosis (MS), and Sjögren's syndrome, and rheumatoid arthritis.
• As used herein, "treating" or "treatment" cover the treatment of a disease-state in a mammal, particularly in a human, and include: (a) preventing the disease-state from occurring in a mammal, in particular, when such mammal is predisposed to the disease-state but has not yet been diagnosed as having it; (b) inhibiting the disease-state, i.e., arresting its development; and/or (c) relieving the disease-state, i.e., causing regression of the disease state.
• The compounds of the present invention are intended to include all isotopes of atoms occurring in the present compounds. Isotopes include those atoms having the same atomic number but different mass numbers. By way of general example and without limitation, isotopes of hydrogen include deuterium (D) and tritium (T). Isotopes of carbon include ¹³C and ¹⁴C. Isotopically-labeled compounds of the invention can generally be prepared by conventional techniques known to those skilled in the art or by processes analogous to those described herein, using an appropriate isotopically-labeled reagent in place of the non-labeled reagent otherwise employed. For example, methyl (-CH₃) also includes deuterated methyl groups such as -CD₃.
UTILITY
• The human immune system has evolved to defend the body from microorganisms, viruses, and parasites that can cause infection, disease or death. Complex regulatory mechanisms ensure that the various cellular components of the immune system target the foreign substances or organisms, while not causing permanent or significant damage to the individual. While the initiating events are not well understood at this time, in autoimmune disease states the immune system directs its inflammatory response to target organs in the afflicted individual. Different autoimmune diseases are typically characterized by the predominate or initial target organ or tissues affected; such as the joint in the case of rheumatoid arthritis, the thyroid gland in the case of Hashimoto's thyroiditis, the central nervous system in the case of multiple sclerosis, the pancreas in the case of type I diabetes, and the bowel in the case of inflammatory bowel disease.
• The compounds of the invention inhibit signaling through Toll-like receptor 7, or 8, or 9 (TLR7, TLR8, TLR9) or combinations thereof. Accordingly, compounds of Formula (I) have utility in treating conditions associated with the inhibition of signaling through one or more of TLR7, TLR8, or TLR9. Such conditions include TLR7, TLR8, or TLR9 receptor associated diseases in which cytokine levels are modulated as a consequence of intracellular signaling.
• As used herein, the terms "treating" or "treatment" encompass the treatment of a disease state in a mammal, particularly in a human, and include: (a) preventing or delaying the occurrence of the disease state in a mammal, in particular, when such mammal is predisposed to the disease state but has not yet been diagnosed as having it; (b) inhibiting the disease state, i.e., arresting its development; and/or (c) achieving a full or partial reduction of the symptoms or disease state, and/or alleviating, ameliorating, lessening, or curing the disease or disorder and/or its symptoms.
• In view of their activity as selective inhibitors of TLR7, TLR8, or TLR9, compounds of Formula (I) are useful in treating TLR7, TLR8, or TLR9 family receptor associated diseases, but not limited to, inflammatory diseases such as Crohn's disease, ulcerative colitis, asthma, graft versus host disease, allograft rejection, chronic obstructive pulmonary disease; autoimmune diseases such as Graves' disease, rheumatoid arthritis, systemic lupus erythematosus, lupus nephritis, cutaneous lupus, psoriasis; auto-inflammatory diseases including Cryopyrin-Associated Periodic Syndromes (CAPS), TNF Receptor Associated Periodic Syndrome (TRAPS), Familial Mediterranean Fever (FMF), adult onset stills, systemic onset juvenile idiopathic arthritis, gout, gouty arthritis; metabolic diseases including type 2 diabetes, atherosclerosis, myocardial infarction; destructive bone disorders such as bone resorption disease, osteoarthritis, osteoporosis, multiple myeloma-related bone disorder; proliferative disorders such as acute myelogenous leukemia, chronic myelogenous leukemia; angiogenic disorders such as angiogenic disorders including solid tumors, ocular neovascularization, and infantile haemangiomas; infectious diseases such as sepsis, septic shock, and Shigellosis; neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, cerebral ischemias or neurodegenerative disease caused by traumatic injury, oncologic and viral diseases such as metastatic melanoma, Kaposi's sarcoma, multiple myeloma, and HIV infection and CMV retinitis, AIDS, respectively.
• More particularly, the specific conditions or diseases that may be treated with the inventive compounds include, without limitation, pancreatitis (acute or chronic), asthma, allergies, adult respiratory distress syndrome, chronic obstructive pulmonary disease, glomerulonephritis, rheumatoid arthritis, systemic lupus erythematosus, scleroderma, chronic thyroiditis, Graves' disease, autoimmune gastritis, diabetes, autoimmune hemolytic anemia, autoimmune neutropenia, thrombocytopenia, atopic dermatitis, chronic active hepatitis, myasthenia gravis, multiple sclerosis, inflammatory bowel disease, ulcerative colitis, Crohn's disease, psoriasis, graft vs. host disease, inflammatory reaction induced by endotoxin, tuberculosis, atherosclerosis, muscle degeneration, cachexia, psoriatic arthritis, Reiter's syndrome, gout, traumatic arthritis, rubella arthritis, acute synovitis, pancreatic β-cell disease; diseases characterized by massive neutrophil infiltration; rheumatoid spondylitis, gouty arthritis and other arthritic conditions, cerebral malaria, chronic pulmonary inflammatory disease, silicosis, pulmonary sarcoidosis, bone resorption disease, allograft rejections, fever and myalgias due to infection, cachexia secondary to infection, keloid formation, scar tissue formation, ulcerative colitis, pyresis, influenza, osteoporosis, osteoarthritis, acute myelogenous leukemia, chronic myelogenous leukemia, metastatic melanoma, Kaposi's sarcoma, multiple myeloma, sepsis, septic shock, and Shigellosis; Alzheimer's disease, Parkinson's disease, cerebral ischemias or neurodegenerative disease caused by traumatic injury; angiogenic disorders including solid tumors, ocular neovascularization, and infantile haemangiomas; viral diseases including acute hepatitis infection (including hepatitis A, hepatitis B and hepatitis C), HIV infection and CMV retinitis, AIDS, ARC or malignancy, and herpes; stroke, myocardial ischemia, ischemia in stroke heart attacks, organ hypoxia, vascular hyperplasia, cardiac and renal reperfusion injury, thrombosis, cardiac hypertrophy, thrombin-induced platelet aggregation, endotoxemia and/or toxic shock syndrome, conditions associated with prostaglandin endoperoxidase syndase-2, and pemphigus vulgaris. Included in the present invention are embodiments in which the condition is selected from lupus including lupus nephritis and systemic lupus erythematosus (SLE), Crohn's disease, ulcerative colitis, allograft rejection, rheumatoid arthritis, psoriasis, ankylosing spondylitis, psoriatic arthritis, and pemphigus vulgaris. Also included are embodiments in which the condition is selected from ischemia reperfusion injury, including cerebral ischemia reperfusions injury arising from stroke and cardiac ischemia reperfusion injury arising from myocardial infarction. Another embodiment is one in which the condition is multiple myeloma.
• In one embodiment, the compounds of Formula (I) are useful in treating cancer, including Waldenstrom's Macroglobulinemia (WM), diffuse large B cell lymphoma (DLBCL), chronic lymphocytic leukemia (CLL), cutaneous diffuse large B cell lymphoma, and primary CNS lymphoma.
• In addition, the TLR7, TLR8, or TLR9 inhibitors of the present invention inhibit the expression of inducible pro-inflammatory proteins such as prostaglandin endoperoxide synthase-2 (PGHS-2), also referred to as cyclooxygenase-2 (COX-2), IL-1, IL-6, IL-18, chemokines. Accordingly, additional TLR7/8/9 associated conditions include edema, analgesia, fever and pain, such as neuromuscular pain, headache, pain caused by cancer, dental pain and arthritis pain. The inventive compounds also may be used to treat veterinary viral infections, such as lentivirus infections, including, but not limited to equine infectious anemia virus; or retrovirus infections, including feline immunodeficiency virus, bovine immunodeficiency virus, and canine immunodeficiency virus.
• The present invention thus provides at least one compound of Formula (I) or a salt thereof for use in treating such conditions, in a subject in need thereof. "Therapeutically effective amount" is intended to include an amount of a compound of the present invention that is effective when administered alone or in combination to inhibit autoimmune disease or chronic inflammatory disease.
• The embodiments for treating TLR7, TLR8, or TLR9 associated conditions may comprise administering compounds of Formula (I) alone or in combination with each other and/or other suitable therapeutic agents useful in treating such conditions. Accordingly, "therapeutically effective amount" is also intended to include an amount of the combination of compounds claimed that is effective to inhibit TLR7, TLR8, or TLR9 and/or treat diseases associated with TLR7, TLR8, or TLR9.
• Exemplary of such other therapeutic agents include corticosteroids, rolipram, calphostin, cytokine-suppressive anti-inflammatory drugs (CSAIDs), Interleukin-10, glucocorticoids, salicylates, nitric oxide, and other immunosuppressants; nuclear translocation inhibitors, such as deoxyspergualin (DSG); non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, celecoxib and rofecoxib; steroids such as prednisone or dexamethasone; antiviral agents such as abacavir; antiproliferative agents such as methotrexate, leflunomide, FK506 (tacrolimus, PROGRAF^®); anti-malarials such as hydroxychloroquine; cytotoxic drugs such as azathiprine and cyclophosphamide; TNF-α inhibitors such as tenidap, anti-TNF antibodies or soluble TNF receptor, and rapamycin (sirolimus or RAPAMUNE^®) or derivatives thereof.
• The above other therapeutic agents, when employed in combination with the compounds of the present invention, may be used, for example, in those amounts indicated in the Physicians' Desk Reference (PDR) or as otherwise determined by one of ordinary skill in the art. In the embodiments of the present invention, such other therapeutic agent(s) may be administered prior to, simultaneously with, or following the administration of the inventive compounds. The present invention also provides pharmaceutical compositions capable of treating TLR7/8/9 receptor-associated conditions, including IL-1 family receptor-mediated diseases as described above.
• The inventive compositions may contain other therapeutic agents as described above and may be formulated, for example, by employing conventional solid or liquid vehicles or diluents, as well as pharmaceutical additives of a type appropriate to the mode of desired administration (e.g., excipients, binders, preservatives, stabilizers, flavors, etc.) according to techniques such as those well known in the art of pharmaceutical formulation.
• Accordingly, the present invention further includes compositions comprising one or more compounds of Formula (I) and a pharmaceutically acceptable carrier.
• A "pharmaceutically acceptable carrier" refers to media generally accepted in the art for the delivery of biologically active agents to animals, in particular, mammals. Pharmaceutically acceptable carriers are formulated according to a number of factors well within the purview of those of ordinary skill in the art. These include without limitation the type and nature of the active agent being formulated; the subject to which the agent-containing composition is to be administered; the intended route of administration of the composition; and, the therapeutic indication being targeted. Pharmaceutically acceptable carriers include both aqueous and non-aqueous liquid media, as well as a variety of solid and semi-solid dosage forms. Such carriers can include a number of different ingredients and additives in addition to the active agent, such additional ingredients being included in the formulation for a variety of reasons, e.g., stabilization of the active agent, binders, etc., well known to those of ordinary skill in the art. Descriptions of suitable pharmaceutically acceptable carriers, and factors involved in their selection, are found in a variety of readily available sources such as, for example, Remington's Pharmaceutical Sciences, 17th Edition (1985).
• Compounds in accordance with Formula (I) can be administered by any means suitable for the condition to be treated, which can depend on the need for site-specific treatment or quantity of Formula (I) compound to be delivered.
• Also embraced within this invention is a class of pharmaceutical compositions comprising a compound of Formula (I) and one or more non-toxic, pharmaceutically-acceptable carriers and/or diluents and/or adjuvants (collectively referred to herein as "carrier" materials) and, if desired, other active ingredients. The compounds of Formula (I) may be administered by any suitable route, preferably in the form of a pharmaceutical composition adapted to such a route, and in a dose effective for the treatment intended. The compounds and compositions of the present invention may, for example, be administered orally, mucosally, or parenterally including intravascularly, intravenously, intraperitoneally, subcutaneously, intramuscularly, and intrasternally in dosage unit formulations containing conventional pharmaceutically acceptable carriers, adjuvants, and vehicles. For example, the pharmaceutical carrier may contain a mixture of mannitol or lactose and microcrystalline cellulose. The mixture may contain additional components such as a lubricating agent, e.g. magnesium stearate and a disintegrating agent such as crospovidone. The carrier mixture may be filled into a gelatin capsule or compressed as a tablet. The pharmaceutical composition may be administered as an oral dosage form or an infusion, for example.
• For oral administration, the pharmaceutical composition may be in the form of, for example, a tablet, capsule, liquid capsule, suspension, or liquid. The pharmaceutical composition is preferably made in the form of a dosage unit containing a particular amount of the active ingredient. For example, the pharmaceutical composition may be provided as a tablet or capsule comprising an amount of active ingredient in the range of from about 0.1 to 1000 mg, preferably from about 0.25 to 250 mg, and more preferably from about 0.5 to 100 mg. A suitable daily dose for a human or other mammal may vary widely depending on the condition of the patient and other factors, but, can be determined using routine methods.
• Any pharmaceutical composition contemplated herein can, for example, be delivered orally via any acceptable and suitable oral preparations. Exemplary oral preparations, include, but are not limited to, for example, tablets, troches, lozenges, aqueous and oily suspensions, dispersible powders or granules, emulsions, hard and soft capsules, liquid capsules, syrups, and elixirs. Pharmaceutical compositions intended for oral administration can be prepared according to any methods known in the art for manufacturing pharmaceutical compositions intended for oral administration. In order to provide pharmaceutically palatable preparations, a pharmaceutical composition in accordance with the invention can contain at least one agent selected from sweetening agents, flavoring agents, coloring agents, demulcents, antioxidants, and preserving agents.
• A tablet can, for example, be prepared by admixing at least one compound of Formula (I) with at least one non-toxic pharmaceutically acceptable excipient suitable for the manufacture of tablets. Exemplary excipients include, but are not limited to, for example, inert diluents, such as, for example, calcium carbonate, sodium carbonate, lactose, calcium phosphate, and sodium phosphate; granulating and disintegrating agents, such as, for example, microcrystalline cellulose, sodium crosscarmellose, corn starch, and alginic acid; binding agents, such as, for example, starch, gelatin, polyvinyl-pyrrolidone, and acacia; and lubricating agents, such as, for example, magnesium stearate, stearic acid, and talc. Additionally, a tablet can either be uncoated, or coated by known techniques to either mask the bad taste of an unpleasant tasting drug, or delay disintegration and absorption of the active ingredient in the gastrointestinal tract thereby sustaining the effects of the active ingredient for a longer period. Exemplary water soluble taste masking materials, include, but are not limited to, hydroxypropyl-methylcellulose and hydroxypropyl-cellulose. Exemplary time delay materials, include, but are not limited to, ethyl cellulose and cellulose acetate butyrate.
• Hard gelatin capsules can, for example, be prepared by mixing at least one compound of Formula (I) with at least one inert solid diluent, such as, for example, calcium carbonate; calcium phosphate; and kaolin.
• Soft gelatin capsules can, for example, be prepared by mixing at least one compound of Formula (I) with at least one water soluble carrier, such as, for example, polyethylene glycol; and at least one oil medium, such as, for example, peanut oil, liquid paraffin, and olive oil.
• An aqueous suspension can be prepared, for example, by admixing at least one compound of Formula (I) with at least one excipient suitable for the manufacture of an aqueous suspension. Exemplary excipients suitable for the manufacture of an aqueous suspension, include, but are not limited to, for example, suspending agents, such as, for example, sodium carboxymethylcellulose, methylcellulose, hydroxypropylmethylcellulose, sodium alginate, alginic acid, polyvinyl-pyrrolidone, gum tragacanth, and gum acacia; dispersing or wetting agents, such as, for example, a naturally-occurring phosphatide, e.g., lecithin; condensation products of alkylene oxide with fatty acids, such as, for example, polyoxyethylene stearate; condensation products of ethylene oxide with long chain aliphatic alcohols, such as, for example heptadecaethylene-oxycetanol; condensation products of ethylene oxide with partial esters derived from fatty acids and hexitol, such as, for example, polyoxyethylene sorbitol monooleate; and condensation products of ethylene oxide with partial esters derived from fatty acids and hexitol anhydrides, such as, for example, polyethylene sorbitan monooleate. An aqueous suspension can also contain at least one preservative, such as, for example, ethyl and n-propyl p-hydroxybenzoate; at least one coloring agent; at least one flavoring agent; and/or at least one sweetening agent, including but not limited to, for example, sucrose, saccharin, and aspartame.
• Oily suspensions can, for example, be prepared by suspending at least one compound of Formula (I) in either a vegetable oil, such as, for example, arachis oil; olive oil; sesame oil; and coconut oil; or in mineral oil, such as, for example, liquid paraffin. An oily suspension can also contain at least one thickening agent, such as, for example, beeswax; hard paraffin; and cetyl alcohol. In order to provide a palatable oily suspension, at least one of the sweetening agents already described hereinabove, and/or at least one flavoring agent can be added to the oily suspension. An oily suspension can further contain at least one preservative, including, but not limited to, for example, an anti-oxidant, such as, for example, butylated hydroxyanisol, and alpha-tocopherol.
• Dispersible powders and granules can, for example, be prepared by admixing at least one compound of Formula (I) with at least one dispersing and/or wetting agent; at least one suspending agent; and/or at least one preservative. Suitable dispersing agents, wetting agents, and suspending agents are as already described above. Exemplary preservatives include, but are not limited to, for example, anti-oxidants, e.g., ascorbic acid. In addition, dispersible powders and granules can also contain at least one excipient, including, but not limited to, for example, sweetening agents; flavoring agents; and coloring agents.
• An emulsion of at least one compound of Formula (I) thereof can, for example, be prepared as an oil-in-water emulsion. The oily phase of the emulsions comprising compounds of Formula (I) may be constituted from known ingredients in a known manner. The oil phase can be provided by, but is not limited to, for example, a vegetable oil, such as, for example, olive oil and arachis oil; a mineral oil, such as, for example, liquid paraffin; and mixtures thereof. While the phase may comprise merely an emulsifier, it may comprise a mixture of at least one emulsifier with a fat or an oil or with both a fat and an oil. Suitable emulsifying agents include, but are not limited to, for example, naturally-occurring phosphatides, e.g., soy bean lecithin; esters or partial esters derived from fatty acids and hexitol anhydrides, such as, for example, sorbitan monooleate; and condensation products of partial esters with ethylene oxide, such as, for example, polyoxyethylene sorbitan monooleate. Preferably, a hydrophilic emulsifier is included together with a lipophilic emulsifier which acts as a stabilizer. It is also preferred to include both an oil and a fat. Together, the emulsifier(s) with or without stabilizer(s) make-up the so-called emulsifying wax, and the wax together with the oil and fat make up the so-called emulsifying ointment base which forms the oily dispersed phase of the cream formulations. An emulsion can also contain a sweetening agent, a flavoring agent, a preservative, and/or an antioxidant. Emulsifiers and emulsion stabilizers suitable for use in the formulation of the present invention include Tween 60, Span 80, cetostearyl alcohol, myristyl alcohol, glyceryl monostearate, sodium lauryl sulfate, glyceryl distearate alone or with a wax, or other materials well known in the art.
• The compounds of Formula (I) can, for example, also be delivered intravenously, subcutaneously, and/or intramuscularly via any pharmaceutically acceptable and suitable injectable form. Exemplary injectable forms include, but are not limited to, for example, sterile aqueous solutions comprising acceptable vehicles and solvents, such as, for example, water, Ringer's solution, and isotonic sodium chloride solution; sterile oil-in-water microemulsions; and aqueous or oleaginous suspensions.
• Formulations for parenteral administration may be in the form of aqueous or non-aqueous isotonic sterile injection solutions or suspensions. These solutions and suspensions may be prepared from sterile powders or granules using one or more of the carriers or diluents mentioned for use in the formulations for oral administration or by using other suitable dispersing or wetting agents and suspending agents. The compounds may be dissolved in water, polyethylene glycol, propylene glycol, ethanol, corn oil, cottonseed oil, peanut oil, sesame oil, benzyl alcohol, sodium chloride, tragacanth gum, and/or various buffers. Other adjuvants and modes of administration are well and widely known in the pharmaceutical art. The active ingredient may also be administered by injection as a composition with suitable carriers including saline, dextrose, or water, or with cyclodextrin (i.e. Captisol), cosolvent solubilization (i.e. propylene glycol) or micellar solubilization (i.e. Tween 80).
• The sterile injectable preparation may also be a sterile injectable solution or suspension in a non-toxic parenterally acceptable diluent or solvent, for example as a solution in 1,3-butanediol. Among the acceptable vehicles and solvents that may be employed are water, Ringer's solution, and isotonic sodium chloride solution. In addition, sterile, fixed oils are conventionally employed as a solvent or suspending medium. For this purpose any bland fixed oil may be employed, including synthetic mono- or diglycerides. In addition, fatty acids such as oleic acid find use in the preparation of injectables.
• A sterile injectable oil-in-water microemulsion can, for example, be prepared by 1) dissolving at least one compound of Formula (I) in an oily phase, such as, for example, a mixture of soybean oil and lecithin; 2) combining the Formula (I) containing oil phase with a water and glycerol mixture; and 3) processing the combination to form a microemulsion.
• A sterile aqueous or oleaginous suspension can be prepared in accordance with methods already known in the art. For example, a sterile aqueous solution or suspension can be prepared with a non-toxic parenterally-acceptable diluent or solvent, such as, for example, 1,3-butane diol; and a sterile oleaginous suspension can be prepared with a sterile non-toxic acceptable solvent or suspending medium, such as, for example, sterile fixed oils, e.g., synthetic mono- or diglycerides; and fatty acids, such as, for example, oleic acid.
• Pharmaceutically acceptable carriers, adjuvants, and vehicles that may be used in the pharmaceutical compositions of this invention include, but are not limited to, ion exchangers, alumina, aluminum stearate, lecithin, self-emulsifying drug delivery systems (SEDDS) such as d-alpha-tocopherol polyethyleneglycol 1000 succinate, surfactants used in pharmaceutical dosage forms such as Tweens, polyethoxylated castor oil such as CREMOPHOR surfactant (BASF), or other similar polymeric delivery matrices, serum proteins, such as human serum albumin, buffer substances such as phosphates, glycine, sorbic acid, potassium sorbate, partial glyceride mixtures of saturated vegetable fatty acids, water, salts or electrolytes, such as protamine sulfate, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salts, colloidal silica, magnesium trisilicate, polyvinyl pyrrolidone, cellulose-based substances, polyethylene glycol, sodium carboxymethylcellulose, polyacrylates, waxes, polyethylene-polyoxypropylene-block polymers, polyethylene glycol and wool fat. Cyclodextrins such as alpha-, beta-, and gamma-cyclodextrin, or chemically modified derivatives such as hydroxyalkylcyclodextrins, including 2- and 3-hydroxypropyl-cyclodextrins, or other solubilized derivatives may also be advantageously used to enhance delivery of compounds of the formulae described herein.
• The pharmaceutically active compounds of this invention can be processed in accordance with conventional methods of pharmacy to produce medicinal agents for administration to patients, including humans and other mammals. The pharmaceutical compositions may be subjected to conventional pharmaceutical operations such as sterilization and/or may contain conventional adjuvants, such as preservatives, stabilizers, wetting agents, emulsifiers, buffers etc. Tablets and pills can additionally be prepared with enteric coatings. Such compositions may also comprise adjuvants, such as wetting, sweetening, flavoring, and perfuming agents.
• The amounts of compounds that are administered and the dosage regimen for treating a disease condition with the compounds and/or compositions of this invention depends on a variety of factors, including the age, weight, sex, the medical condition of the subject, the type of disease, the severity of the disease, the route and frequency of administration, and the particular compound employed. Thus, the dosage regimen may vary widely, but can be determined routinely using standard methods. A daily dose of about 0.001 to 100 mg/kg body weight, preferably between about 0.0025 and about 50 mg/kg body weight and most preferably between about 0.005 to 10 mg/kg body weight, may be appropriate. The daily dose can be administered in one to four doses per day. Other dosing schedules include one dose per week and one dose per two day cycle.
• For therapeutic purposes, the active compounds of this invention are ordinarily combined with one or more adjuvants appropriate to the indicated route of administration. If administered orally, the compounds may be admixed with lactose, sucrose, starch powder, cellulose esters of alkanoic acids, cellulose alkyl esters, talc, stearic acid, magnesium stearate, magnesium oxide, sodium and calcium salts of phosphoric and sulfuric acids, gelatin, acacia gum, sodium alginate, polyvinylpyrrolidone, and/or polyvinyl alcohol, and then tableted or encapsulated for convenient administration. Such capsules or tablets may contain a controlled-release formulation as may be provided in a dispersion of active compound in hydroxypropylmethyl cellulose.
• Pharmaceutical compositions of this invention comprise at least one compound of Formula (I) and optionally an additional agent selected from any pharmaceutically acceptable carrier, adjuvant, and vehicle. Alternate compositions of this invention comprise a compound of the Formula (I) described herein, and a pharmaceutically acceptable carrier, adjuvant, or vehicle.
• The present invention also encompasses an article of manufacture. As used herein, article of manufacture is intended to include, but not be limited to, kits and packages. The article of manufacture of the present invention, comprises: (a) a first container; (b) a pharmaceutical composition located within the first container, wherein the composition, comprises: a first therapeutic agent, comprising: a compound of the present invention or a pharmaceutically acceptable salt form thereof; and (c) a package insert stating that the pharmaceutical composition can be used for the treatment of an inflammatory disorder and/or an autoimmune disease (as defined previously). In another embodiment, the package insert states that the pharmaceutical composition can be used in combination (as defined previously) with a second therapeutic agent to treat an inflammatory disorder and/or an autoimmune disease. The article of manufacture can further comprise: (d) a second container, wherein components (a) and (b) are located within the second container and component (c) is located within or outside of the second container. Located within the first and second containers means that the respective container holds the item within its boundaries.
• The first container is a receptacle used to hold a pharmaceutical composition. This container can be for manufacturing, storing, shipping, and/or individual/bulk selling. First container is intended to cover a bottle, jar, vial, flask, syringe, tube (e.g., for a cream preparation), or any other container used to manufacture, hold, store, or distribute a pharmaceutical product.
• The second container is one used to hold the first container and, optionally, the package insert. Examples of the second container include, but are not limited to, boxes (e.g., cardboard or plastic), crates, cartons, bags (e.g., paper or plastic bags), pouches, and sacks. The package insert can be physically attached to the outside of the first container via tape, glue, staple, or another method of attachment, or it can rest inside the second container without any physical means of attachment to the first container. Alternatively, the package insert is located on the outside of the second container. When located on the outside of the second container, it is preferable that the package insert is physically attached via tape, glue, staple, or another method of attachment. Alternatively, it can be adjacent to or touching the outside of the second container without being physically attached.
• The package insert is a label, tag, marker, etc. that recites information relating to the pharmaceutical composition located within the first container. The information recited will usually be determined by the regulatory agency governing the area in which the article of manufacture is to be sold (e.g., the United States Food and Drug Administration). In one embodiment, the package insert specifically recites the indications for which the pharmaceutical composition has been approved. The package insert may be made of any material on which a person can read information contained therein or thereon. For example, the package insert is a printable material (e.g., paper, plastic, cardboard, foil, adhesive-backed paper or plastic, etc.) on which the desired information has been formed (e.g., printed or applied).
METHODS OF PREPARATION
• The compounds of the present invention can be prepared in a number of ways well known to one skilled in the art of organic synthesis. The compounds of the present invention can be synthesized using the methods described below, together with synthetic methods known in the art of synthetic organic chemistry, or variations thereon as appreciated by those skilled in the art. Preferred methods include, but are not limited to, those described below.
• The compounds of this invention may be prepared using the reactions and techniques described in this section. The reactions are performed in solvents appropriate to the reagents and materials employed and are suitable for the transformations being effected. Also, in the description of the synthetic methods described below, it is to be understood that all proposed reaction conditions, including choice of solvent, reaction atmosphere, reaction temperature, duration of the experiment and work up procedures, are chosen to be the conditions standard for that reaction, which should be readily recognized by one skilled in the art. It is understood by one skilled in the art of organic synthesis that the functionality present on various portions of the molecule must be compatible with the reagents and reactions proposed. Such restrictions to the substituents that are compatible with the reaction conditions will be readily apparent to one skilled in the art and alternate methods must then be used. This will sometimes require a judgment to modify the order of the synthetic steps or to select one particular process scheme over another in order to obtain a desired compound of the invention. It will also be recognized that another major consideration in the planning of any synthetic route in this field is the judicious choice of the protecting group used for protection of the reactive functional groups present in the compounds described in this invention. An authoritative account describing the many alternatives to the trained practitioner is Greene and Wuts (Protective Groups In Organic Synthesis, Third Edition, Wiley and Sons, 1999).
EXAMPLES
• Preparation of compounds of Formula (I), and intermediates used in the preparation of compounds of Formula (I), can be prepared using procedures shown in the following Examples and related procedures. The methods and conditions used in these examples, and the actual compounds prepared in these Examples, are not meant to be limiting, but are meant to demonstrate how the compounds of Formula (I) can be prepared. Starting materials and reagents used in these examples, when not prepared by a procedure described herein, are generally either commercially available, or are reported in the chemical literature, or may be prepared by using procedures described in the chemical literature.
ABBREVIATIONS

Ac

acetyl

ACN

acetonitrile

AcOH

acetic acid

anhyd.

anhydrous

aq.

aqueous

Bn

benzyl

Bu

butyl

Boc

tert-butoxycarbonyl

CV

Column Volumes

DCE

dichloroethane

DCM

dichloromethane

DMAP

dimethylaminopyridine

DMF

dimethylformamide

DMSO

dimethylsulfoxide

EDC

1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride

EtOAc

ethyl acetate

Et

ethyl

EtOH

ethanol

H or H2

hydrogen

h, hr or hrs

hour(s)

HCTU

O-(6-Chlorobenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate

hex

hexane

i

iso

IPA

isopropyl alcohol

HOAc

acetic acid

HCl

hydrochloric acid

HPLC

high pressure liquid chromatography

LC

liquid chromatography

M

molar

mM

millimolar

Me

methyl

MeOH

methanol

MHz

megahertz

min.

minute(s)

mins

minute(s)

M+1

(M+H)⁺

MS

mass spectrometry

n or N

normal

NBS

n-bromosuccinimide

nm

nanometer

nM

nanomolar

NMP

N-methylpyrrolidine

Pd/C

palladium on carbon

PdCl2(dppf)2

[1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II)

Pd(PPh3)4

tetrakis(triphenylphosphine)palladium

Ph

phenyl

PPh3

triphenylphosphine

Pr

propyl

PSI

pounds per square inch

PyBOP

bromotripyrrolidinophosphonium hexafluorophosphate

Ret Time

retention time

sat.

saturated

SFC

supercritical fluid chromatography

TEA

triethylamine

TFA

trifluoroacetic acid

THF

tetrahydrofuran

• Analytical and Preparative HPLC conditions:
• QC-ACN-AA-XB: Column: Waters Acquity UPLC BEH C18, 2.1 x 50 mm, 1.7 µm particles; Mobile Phase A: 5:95 acetonitrile:water with 10 mM ammonium acetate;
• Mobile Phase B: 95:5 acetonitrile:water with 10 mM ammonium acetate; Temperature:
  50 °C; Gradient: 0-100% B over 3 minutes, then a 0.75 minute hold at 100% B; Flow: 1.0 mL/min; Detection: UV at 220 nm.
• QC-ACN-TFA-XB: Column: Waters Acquity UPLC BEH C18, 2.1 x 50 mm, 1.7 µm particles; Mobile Phase A: 5:95 acetonitrile:water with 0.1% trifluoroacetic acid; Mobile Phase B: 95:5 acetonitrile:water with 0.1% trifluoroacetic acid; Temperature: 50 °C; Gradient: 0-100% B over 3 minutes, then a 0.75 minute hold at 100% B; Flow: 1.0 mL/min; Detection: UV at 220 nm.
• Method A1: L3 Acquity: Column: (LCMS) UPLC BEH C18, 2.1 x 50 mm, 1.7 µm particles; Mobile Phase: (A) water; (B) acetonitrile; Buffer: 0.05% TFA; Gradient Range: 2%-98% B (0 to 1 min) 98%B (to 1.5 min) 98%-2% B (to 1.6 min); Gradient Time: 1.6 min; Flow Rate: 0.8 mL/min; Analysis Time: 2.2 min; Detection: Detector 1: UV at 220 nm; Detector 2: MS (ESI⁺).
• Method B1: L2 Aquity; Column: (LCMS) UPLC BEH C18, 2.1 x 50 mm, 1.7 µm particles; Mobile Phase: (A) water; (B) acetonitrile; Buffer: 0.05% TFA; Gradient Range: 2%-98% B (0 to 1 min), 98%-2% B (to 1.5 min); Gradient Time: 1.8 min; Flow Rate: 0.8 mL/min; Analysis Time: 2.2 min; Detection: Detector 1: UV at 220 nm; Detector 2: MS (ESI⁺).
• Method C1 SCP: Column: Waters Acquity UPLC BEH C18, 2.1 x 50 mm, 1.7 µm particles; Mobile Phase A: 5:95 acetonitrile:water with 10 mM ammonium acetate; Mobile Phase B: 95:5 acetonitrile:water with 10 mM ammonium acetate. Temperature: 50 °C; Gradient: 0-100% B over 3 minutes, then a 0.75 minute hold at 100% B; Flow:
  1.11 mL/min; Detection: UV at 220 nm.
• Method D1 SCP: Column: Waters Acquity UPLC BEH C18, 2.1 x 50 mm, 1.7 µm particles; Mobile Phase A: 5:95 acetonitrile:water with 0.1% trifluoroacetic acid; Mobile Phase B: 95:5 acetonitrile:water with 0.1% trifluoroacetic acid; Temperature: 50 °C; Gradient: 0-100% B over 3 minutes, then a 0.75-minute hold at 100% B; Flow: 1.11 mL/min; Detection: UV at 220 nm.
• Method D2 SCP: Column: XBridge C18, 19 x 200 mm, 5 µm particles;
  Mobile Phase A: 5:95 acetonitrile: water with 10-mM ammonium acetate; Mobile Phase B: 95:5 acetonitrile: water with 10 mM ammonium acetate; Gradient: 10-50% B over 20 minutes, then a 5 minute hold at 100% B; Flow: 20 mL/min. Detection: UV at 220 nm. Method D3 SCP: Column: XBridge C18, 19 x 200 mm, 5 µm particles; Mobile Phase A: 5:95 acetonitrile: water with 0.1% trifluoroacetic acid; Mobile Phase B: 95:5 acetonitrile: water with 0.1% trifluoroacetic acid; Gradient: 6-46% B over 20 minutes, then a 4 minute hold at 100% B; Flow: 20 mL/min. Detection: UV at 220 nm.
• Method E1 iPAC: Column: Waters Xbridge C18 4.6 x 50 mm 5 µm particles; Mobile Phase A: 5:95 acetonitrile:water with 10 mM ammonium acetate; Mobile Phase B: 95:5 acetonitrile:water with 10 mM ammonium acetate. Temperature: 50 °C; Gradient: 0-100% B over 1 minute; Flow: 4 mL/min; Detection: UV at 220 nm.
• Method F1 iPAC: Column: Waters Acquity BEH C18 2.1x50 mm 1.7 µm particles; Mobile Phase A: 5:95 acetonitrile:water with 0.1% trifluoroacetic acid; Mobile Phase B: 95:5 acetonitrile:water with 0.1% trifluoroacetic acid; Temperature: 50 °C; Gradient: 0-100% B over 2.20 minutes; Flow: 0.800 mL/min; Detection: UV at 220 nm.
• (A): Column-Ascentis Express C18 (50 x 2.1 mm-2.7 µm) Mphase A: 10 mM NH₄COOH in water: ACN (98:02); Mphase B: 10 mM NH₄COOH in water: ACN (02:98), Gradient: 0-100% B over 3 minutes, Flow = 1 mL/min.
• (B): Waters Acquity BEH C18 (2.1 x 50 mm) 1.7 micron; Buffer: 5 mM ammonium acetate pH 5 adjusted with HCOOH, Solvent A: Buffer:ACN (95:5), Solvent B: Buffer:ACN (5:95), Method:%B: 0 min-5%: 1.1 min -95%: 1.7 min-95%, Flow: 0.8 mL/min.
• (C): Column-Ascentis Express C18 (50 x 2.1 mm, 2.7 µm) Mobile phase A: 0.1% HCOOH in water; Mobile phase B: ACN. Temperature: 50 °C; Gradient: 0-100% B over 3 minutes; Flow rate: 1.0 mL/min.
• (D): Kinetex XB-C18 (75 x 3 mm) 2.6 micron; Solvent A: 10 mM ammonium formate in water: acetonitrile (98:02); Mobile Phase B: 10 mM ammonium formate in water: acetonitrile (02:98); Temperature: 50 °C; Gradient: 0-100% B over 3 minutes; Flow rate: 1.1 mL/min; Detection: UV at 220 nm.
• (E): Column: Ascentis Express C18 (50 x 2.1)mm, 2.7 µm; Mobile Phase A: 5:95 acetonitrile: water with 10 mM NH₄OAc; Mobile Phase B: 95:5 acetonitrile: water with 10 mM NH₄OAc; Temperature: 50 °C; Gradient: 0-100% B over 3 minutes; Flow: 1.1 mL/min.
• (F): Column: Ascentis Express C18 (50 x 2.1)mm, 2.7 µm; Mobile Phase A: 5:95 acetonitrile: water with 0.1% TFA; Mobile Phase B: 95:5 acetonitrile: water with 0.1% TFA; Temperature: 50 °C; Gradient: 0-100%B over 3 minutes; Flow: 1.1 mL/min.
• (G): Column: Waters Acquity UPLC BEH C18 (2.1 x 50 mm), 1.7 micron; Solvent A = 100% water with 0.05% TFA; Solvent B = 100% acetonitrile with 0.05% TFA; gradient = 2-98% B over 1 minute, then a 0.5 minute hold at 98% B; Flow rate: 0.8 mL/min; Detection: UV at 220 nm.
• (H): Column: Acentis Express C18 (50 x 2.1 mm) 1.7 µm, Acentis C8 NH₄COOH 5 min. M, Mobile Phase A: 10 mM ammonium formate: ACN (98:2), Mobile Phase B: 10 mM ammonium formate: ACN (2:98), gradient: 20%-100% B (0-4 min); 100% B (4-4.6 min); Flow: 1 mL/min
• (I) Column: Sunfire C18 (4.6 x 150) mm, 3.5 µm; Mobile Phase A: 5:95 acetonitrile: water with 0.05% TFA; Mobile Phase B: 95:5 acetonitrile: water with 0.05% TFA; Temperature: 50 °C; Gradient:10-100%B over 12 minutes; Flow:1 mL/min.
• (J) Column: Sunfire C18 (4.6 x 150)mm, 3.5 µm; Mobile Phase A: 5:95 acetonitrile: water with 0.05% TFA; Mobile Phase B: 95:5 acetonitrile: water with 0.05% TFA;
• (K) Waters Acquity SDS Mobile Phase: A: water B: ACN; 5%-95%B in 1 min; Gradient Range: 50%-98% B (0-0.5 min); 98%B (0.5 min-1 min); 98%-2% B (1-1.1 min); Run time: 1.2 min; Flow Rate: 0.7 mL/min; Analysis Time: 1.7 min; Detection: Detector 1: UV at 220 nm; Detector 2: MS (ES⁺).
• (L) Acquity UPLC BEH C18 (3.0 x 50 mm) 1.7 µm. Buffer: 5 mM ammonium acetate Mobile phase A: Buffer:ACN (95:5); Mobile phase B:Buffer:ACN (5:95) Method: %B: 0 min-20%:1.1 min -90%:1.7 min-90%. Run time: 2.25 min; Flow Rate: 0.7 mL/min; Detection: Detector 1: UV at 220 nm; Detector 2: MS (ES⁺).
• (M): Kinetex SBC18 (4.6 x 50 mm) 5 micron; Solvent A: 10 mM ammonium formate in water: acetonitrile (98:02); Mobile Phase B: 10 mM ammonium formate in water: acetonitrile (02:98); Temperature: 50 °C; Gradient: 30-100% B (0-4 min), 100% B (4-4.6 min), 100-30% B (4.6-4.7 min), 30% B (4.7-5.0 min); Flow rate: 1.5 mL/min; Detection: UV at 220 nm.
• (N): Column-Ascentis Express C18 (50 x 2.1 mm-2.7 µm) Mphase A: 10 mM NH₄COOH in water: ACN (98:02); Mphase B: 10 mM NH₄COOH in water: ACN (02:98), Gradient: 0-100% B (0-1.7 minutes); 100% B (1.7-3.4 minutes). Flow = 1 mL/min.
• (O) Waters Acquity SDS Column BEH C18 (2.1 x 50 mm) 1.7 µm. Phase A: buffer in water; Mphase B: buffer in ACN, Gradient: 20-98% B (0-1.25 minutes); 98% B (1.25-1.70 minutes); 98%-2% B (1.70-1.75 minutes); Flow = 0.8 mL/min.
• (Q): Column: XBridge BEH XP C18 (50 x 2.1) mm, 2.5 µm; Mobile Phase A: 5:95 acetonitrile: water with 0.1% TFA; Mobile Phase B: 95:5 acetonitrile: water with 0.1% TFA; Temperature: 50 °C; Gradient: 0-100%B over 3 minutes; Flow: 1.1 mL/min.
(TS): Column: Waters Acquity UPLC BEH C18 (2.1 x 50 mm), 1.7 micron; Solvent A = 100% water with 0.05% TFA; Solvent B = 100% acetonitrile with 0.05% TFA; gradient = 2-98% B over 1 minute, then a 0.5-minute hold at 98% B; Flow rate: 0.8 mL/min; Detection: UV at 254 nm. EXAMPLE 1 6-(3-isopropyl-4-methyl-5-(piperidin-4-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine
• 
Intermediate 1A: 3-bromo-4-methyl-5-nitropyridin-2-ol
• 
• To a solution of 4-methyl-5-nitropyridin-2-ol (4.0 g, 26.0 mmol) in acetic acid (40 mL) was added bromine (1.604 mL, 31.1 mmol) dropwise at 0 °C. The reaction mixture was stirred for 3 h at room temperature. The reaction mass was concentrated, ice cold water was added to the residue, the mixture was stirred for 5 min and filtered to afford 3-bromo-4-methyl-5-nitropyridin-2-ol (5.2 g, 22.32 mmol, 86% yield) as an off-white solid. LCMS retention time 1.082 min [D]. MS m/z: 235 [M+2H]⁺.
Intermediate 1B: 3-bromo-2-chloro-4-methyl-5-nitropyridine
• 
• To a solution of 3-bromo-4-methyl-5-nitropyridin-2-ol (5.2 g, 22.32 mmol) in acetonitrile (50 mL) were added POCl₃ (20.80 mL, 223 mmol) and DIPEA (3.90 mL, 22.32 mmol) at 0 °C. The reaction mixture was stirred for 3 h at 80 °C. The reaction mass was concentrated, ice cold water and solid NaHCOs were added to the residue, extracted with EtOAc (2 x 50 mL), the organic layer was washed with brine solution, dried over Na₂SO₄, concentrated and purified over 40 g silica column, the compound was eluted in 15% EA in hexane, the fractions were collected and concentrated to afford 3-bromo-2-chloro-4-methyl-5-nitropyridine (0.48 g, 1.909 mmol, 89% yield) as an off-white solid. LCMS retention time 2.619 min [D]. MS m/z: 248.9 [M-2H]⁺.
Intermediate 1C: (E)-2-(3-bromo-2-chloro-5-nitropyridin-4-yl)-N,N-dimethylethen-1-amine
• 
• A solution of 3-bromo-2-chloro-4-methyl-5-nitropyridine (8.7 g, 34.6 mmol) in DMF-DMA (46.3 mL, 346 mmol) was stirred for 16 h at 45 °C. The reaction mass was concentrated under high vacuum, then purified over silica gel column, the compound was eluted in 30% EA in hexanes, the fractions were collected and concentrated to afford (E)-2-(3-bromo-2-chloro-5-nitropyridin-4-yl)-N,N-dimethylethenamine (10.0 g, 32.6 mmol, 94% yield) as a brown solid. LCMS retention time 2.685 min [D]. MS m/z: 306.0 [M+2H]⁺.
Intermediate 1D: 4-bromo-5-chloro-1H-pyrrolo[2,3-c]pyridine
• 
• To a solution of (E)-2-(3-bromo-2-chloro-5-nitropyridin-4-yl)-N,N-dimethylethenamine (4.2 g, 13.70 mmol) in acetic acid (40 mL) was added iron (3.83 g, 68.5 mmol) at room temperature. The reaction mixture was stirred at 60 °C for 3 h. The reaction mixture was cooled to room temperature, quenched with cold water (80 mL), extracted with DCM (3 X 50 mL), combined organic layers were dried over Na₂SO₄ and concentrated to get crude compound. The crude compound was purified by silica gel column chromatography, the compound was eluted in 0 to 30% EA in hexane, the fractions were collected and concentrated to afford 4-bromo-5-chloro-1H-pyrrolo[2,3-c] pyridine (2.6 g, 11.23 mmol, 82% yield) as light brown solid. LCMS retention time 1.992 min [D]. MS m/z: 233.0 [M+2H]⁺.
Intermediate 1E: 5-chloro-4-methyl-1H-pyrrolo[2,3-c]pyridine
• 
• To a solution of 4-bromo-5-chloro-1H-pyrrolo[2,3-c]pyridine (2.6 g, 11.23 mmol) and methylboronic acid (2.017 g, 33.7 mmol) in mixture of THF (2 mL) and water (0.2 mL) was added potassium phosphate tribasic (7.15 g, 33.7 mmol). The reaction mixture was purged with nitrogen for 5 mins, then PdCl₂(dppf)-CH₂Cl₂ adduct (0.917 g, 1.123 mmol) was added. The reaction mixture was purged again for 2 mins. The reaction mixture was heated in a sealed tube at 75 °C for 8 h. The reaction mixture was diluted with EtOAc (50 mL), washed with water (30 mL), brine (10 mL), dried (Na₂SO₄) and concentrated to get crude material. The crude material was purified by silica gel chromatography on an ISCO instrument using 24 g silica column, the compound was eluted in 30% EtOAc in hexanes, the fractions were collected and concentrated to afford 5-chloro-4-methyl-1H-pyrrolo[2,3-c]pyridine (1.35 g, 8.10 mmol, 72.1 % yield). LCMS retention time 1.623 min [D]. MS m/z: 167.1 [M+H]⁺.
Intermediate 1F: tert-butyl 4-(4-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl)-3,6-dihydro pyridine-1(2H) -carboxylate
• 
• A solution of 5-chloro-4-methyl-1H-pyrrolo[2,3-c]pyridine (1.35 g, 8.10 mmol), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate (2.76 g, 8.91 mmol) and potassium phosphate tribasic (5.16 g, 24.31 mmol) in mixture of THF (20 mL) and water (2 mL) was degassed for 10 min with nitrogen gas. Next, PdCl₂(dppf)-CH₂Cl₂ adduct (0.638 g, 0.810 mmol) was added and the reaction mixture was stirred at 80 °C for 16 h. The reaction mixture was diluted with EtOAc (50 mL), washed with water (30 mL), brine (10 mL), dried (Na₂SO₄) and concentrated to get crude material. The crude material was purified by silica gel chromatography on an ISCO instrument using 24 g silica column, the compound was eluted in 30% EtOAc in hexanes, the fractions were collected and concentrated to afford tert-butyl 4-(4-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl)-5,6-dihydropyridine-1(2H)-carboxylate (2.05 g, 6.54 mmol, 81% yield) as an off-white solid. LCMS retention time 2.077 min [D]. MS m/z: 314.2 [M+H]⁺.
Intermediate 1G: tert-butyl 4-(4-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidine-1-carboxylate
• 
• To a solution of tert-butyl 4-(4-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl)-5,6-dihydropyridine-1(2H)-carboxylate (2.0 g, 6.38 mmol) in MeOH (20 mL) was added Pd/C (0.204 g, 1.915 mmol). The reaction mixture was stirred under hydrogen bladder at room temperature for 16 h. The reaction mass was filtered through celite, washed with MeOH, the filtrates were collected and concentrated to afford tert-butyl 4-(4-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidine-1-carboxylate (1.9 g, 6.02 mmol, 94% yield) as a white solid. LCMS retention time 2.069 min [D]. MS m/z: 316.2 [M+H]⁺.
Intermediate 1H: tert-butyl 4-(3-bromo-4-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl) piperidine-1-carboxylate
• 
• To a solution of tert-butyl 4-(4-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidine-1-carboxylate (1.8 g, 5.71 mmol) in DMF (20 mL) at 0 °C was added a solution of NBS (1.016 g, 5.71 mmol) in DMF (3 mL). The reaction mixture was stirred at room temperature for 3 h. The reaction mass was concentrated, partitioned between EtOAc and water, the two layers were separated, the organic layer was washed with water, brine solution, dried over Na₂SO₄ and concentrated to afford tert-butyl 4-(3-bromo-4-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidine-1-carboxylate (1.8 g, 3.70 mmol, 65% yield) as light brown solid. LCMS retention time 3.077 min [D]. MS m/z: 396.2 [M+2H]⁺.
Intermediate 1I: tert-butyl 3-bromo-5-(1-(tert-butoxycarbonyl)piperidin-4-yl)-4-methyl-1H-pyrrolo[2,3-c]pyridine-1-carboxylate
• 
• To a solution of tert-butyl 4-(3-bromo-4-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl) piperidine-1-carboxylate (1.8 g, 4.56 mmol) in THF (40 mL) at 0 °C were added TEA (1.273 mL, 9.13 mmol), Boc₂O (1.590 mL, 6.85 mmol) and DMAP (0.279 g, 2.282 mmol). The reaction mixture was stirred at room temperature for 6 h. The reaction mass was diluted with EtOAc (50 mL), the organic layer was washed with water and brine solution, dried over Na₂SO₄ and concentrated to get crude compound. The crude compound was purified by silica gel column chromatography, the compound was eluted in 20% EA in hexane, the fractions were collected and concentrated to afford tert-butyl 3-bromo-5-(1-(tert-butoxycarbonyl)piperidin-4-yl)-4-methyl-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (1.5 g, 3.03 mmol, 66% yield) as an off-white solid. LCMS retention time 2.246 min [D]. MS m/z: 496.2 [M+2H]⁺.
Intermediate 11: tert-butyl 5-(1-(tert-butoxycarbonyl)piperidin-4-yl)-4-methyl-3-(prop-1-en-2-yl)-1H-pyrrolo[2,3-c]pyridine-1-carboxylate
• 
• A solution of tert-butyl 3-bromo-5-(1-(tert-butoxycarbonyl)piperidin-4-yl)-4-methyl-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (1.4 g, 2.83 mmol), 4,4,5,5-tetramethyl-2-(prop-1-en-2-yl)-1,3,2-dioxaborolane (0.571 g, 3.40 mmol) and potassium phosphate tribasic (1.803 g, 8.49 mmol) in THF (20 mL) and water (2 mL) solvent mixture was degassed for 10 min with nitrogen. Next, 2nd generation XPhos precatalyst (0.223 g, 0.283 mmol) was added and the reaction mixture was stirred at 80 °C for 16 h. The reaction mixture was diluted with EtOAc (50 mL), washed with water (30 mL), brine (10 mL), dried (Na₂SO₄) and concentrated to get crude material. The crude material was purified by silica gel chromatography on an ISCO instrument using 24 g silica column, the compound was eluted in 25% EtOAc in hexanes, the fractions were collected and concentrated to afford tert-butyl 5-(1-(tert-butoxycarbonyl)piperidin-4-yl)-4-methyl-3-(prop-1-en-2-yl)-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (1.05 g, 2.305 mmol, 81% yield) as an off-white solid. LCMS retention time 0.81 min [D] MS m/z: 456.2 [M+H]⁺.
Intermediate 1K: tert-butyl 5-(1-(tert-butoxycarbonyl)piperidin-4-yl)-3-isopropyl-4-methyl-1H-pyrrolo[2,3-c]pyridine-1-carboxylate
• 
• To a solution of tert-butyl 5-(1-(tert-butoxycarbonyl)piperidin-4-yl)-4-methyl-3-(prop-1-en-2-yl)-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (1.05 g, 2.305 mmol) in ethyl acetate (30 mL) was added Pd/C (0.123 g, 1.152 mmol). The reaction mixture was stirred under hydrogen bladder for 2 h. The reaction mass was filtered through celite, washed with MeOH, the filtrate was collected and concentrated to get crude compound. The crude was purified by silica gel column chromatography, the compound was eluted in 10% EA in hexane, the fractions were collected and concentrated to afford tert-butyl 5-(1-(tert-butoxycarbonyl)piperidin-4-yl)-3-isopropyl-4-methyl-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (0.65 g, 1.419 mmol, 61.6 % yield) as a gummy solid. LCMS retention time 4.761 min [D]. MS m/z: 458.2 [M+H]⁺.
Intermediate 1L: tert-butyl 5-(1-(tert-butoxycarbonyl)piperidin-4-yl)-3-isopropyl-4-methyl-2-(4,4, 5, 5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-c]pyridine-1-carboxylate
• 
• To a solution of tert-butyl 5-(1-(tert-butoxycarbonyl)piperidin-4-yl)-3-isopropyl-4-methyl-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (0.5 g, 1.093 mmol) in THF (12 mL) was added LDA (2.185 mL, 4.37 mmol) at -78 °C. The reaction mixture was stirred at the same temperature for 1.5 h, then 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.892 mL, 4.37 mmol) was added. The reaction mixture was stirred for 1 h at -50 °C. The reaction was quenched with aqueous NH₄Cl. The reaction mixture was extracted with EtOAc, washed with water, brine, dried over Na₂SO₄ and concentrated to get crude compound. The crude was purified by silica gel column chromatography, the compound was eluted in 40% EA in hexane, the fractions were collected and concentrated to afford tert-butyl 5-(1-(tert-butoxycarbonyl)piperidin-4-yl)-3-isopropyl-4-methyl-2-(4,4, 5, 5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (0.4 g, 0.685 mmol, 62.7 % yield) as a semi solid. LCMS retention time 1.48 min [G], MS m/z: 584.5 [M+H]⁺.
Intermediate 1M: tert-butyl 5-(1-(tert-butoxycarbonyl)piperidin-4-yl)-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-methyl-1H-pyrrolo[2,3-c]pyridine-1-carboxylate
• 
• A solution of tert-butyl 5-(1-(tert-butoxycarbonyl)piperidin-4-yl)-3-isopropyl-4-methyl-2-(4,4, 5, 5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (0.4 g, 0.685 mmol), 6-bromo-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (0.172 g, 0.754 mmol) and potassium phosphate tribasic (0.436 g, 2.056 mmol) in 1,4-dioxane (8 mL) and water (1 mL) solvent mixture was degassed for 10 min with nitrogen. Next, PdCl₂(dppf)-CH₂Cl₂ adduct (0.056 g, 0.069 mmol) was added and the reaction mixture was stirred at 90 °C for 8 h. The reaction mixture was diluted with EtOAc (50 mL), washed with water (30 mL), brine (10 mL), dried (Na₂SO₄) and concentrated to get crude material. The crude material was purified by silica gel chromatography on an ISCO instrument using 24 g silica column, compound was eluted in 60% EtOAc in hexanes, the fractions were collected and concentrated to afford tert-butyl 5-(1-(tert-butoxycarbonyl) piperidin-4-yl)-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-methyl-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (0.3 g, 0.496 mmol, 72% yield) as an off-white solid. LCMS retention time 2.779 min [D]. MS m/z: 605.4 [M+H]⁺.
Example 1:
• To a stirred solution of tert-butyl 5-(1-(tert-butoxycarbonyl)piperidin-4-yl)-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-methyl-1H-pyrrolo[2,3-c] pyridine-1-carboxylate (0.3 g, 0.496 mmol) in DCM (1 mL) was added 4 M HCl in dioxane (1.240 mL, 4.96 mmol) at 0 °C. The reaction mixture was stirred at room temperature for 2 h and then concentrated to get crude compound. The crude compound was purified by preparative LCMS using method D2, fractions containing the product were combined and dried using Genevac centrifugal evaporator to afford 6-(3-isopropyl-4-methyl-5-(piperidin-4-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo [1,5-a]pyridine (0.18 g, 0.445 mmol, 90% yield). LCMS retention time 1.356 min [P]. MS m/z: 405.1 [M+H]⁺; ¹H NMR (400 MHz, DMSO-d ₆) δ ppm 11.58 (br. s., 1 H) 8.69 (d, J=1.22 Hz, 1 H) 8.45-8.58 (m, 2 H) 7.14 (d, J=0.98 Hz, 1 H) 4.04 (s, 3 H) 3.58-3.68 (m, 1 H) 3.10-3.20 (m, 2 H) 2.79 (t, J=11.74 Hz, 1 H) 2.68 (s, 3 H) 1.87-1.98 (m, 2 H) 1.82 (s, 3 H) 1.65 (d, J=11.49 Hz, 2 H) 1.21-1.35 (m, 6 H).
EXAMPLE 2 2-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidin-1-yl)-N-methylacetamide
• 
• To a solution of 6-(3-isopropyl-4-methyl-5-(piperidin-4-yl)-1H-pyrrolo[2,3-c] pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (20 mg, 0.049 mmol) and 2-chloro-N-methylacetamide (7.98 mg, 0.074 mmol) in DMF (0.5 mL) and THF (1 mL) solvent mixture was added TEA (0.021 mL, 0.148 mmol) at room temperature. The reaction mixture was stirred for 16 h. The reaction mass was concentrated to get crude compound. The crude compound was purified by preparative LCMS using method D2, fractions containing the product were combined and dried using Genevac centrifugal evaporator to afford 2-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidin-1-yl)-N-methylacetamide (9.1 mg, 0.018 mmol, 36.8 % yield). LCMS retention time 1.632 min [P]. MS m/z: 476.1 [M+H]⁺; ¹H NMR (400 MHz, DMSO-d ₆) δ ppm 11.52 (s, 1 H) 8.69 (d, J=1.22 Hz, 1 H) 8.54 (s, 1 H) 8.50 (s, 1 H) 7.69 (d, J=3.67 Hz, 1 H) 7.14 (s, 1 H) 4.04 (s, 3 H) 3.57-3.66 (m, 1 H) 3.17 (d, J=4.16 Hz, 1 H) 2.87-2.94 (m, 3 H) 2.63-2.69 (m, 4 H) 2.18-2.27 (m, 2 H) 2.02-2.14 (m, 2 H) 1.91 (s, 3 H) 1.62 (d, J=11.98 Hz, 2 H) 1.28 (d, J=7.09 Hz, 6 H).
EXAMPLE 3 6-(4-fluoro-3-isopropyl-5-(piperidin-4-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine
• 
Intermediate 3A: 3-fluoro-4-methyl-5-nitropyridin-2(1H)-one
• 
• To a solution of 4-methyl-5-nitropyridin-2(1H)-one (30 g, 195 mmol) in a mixture of acetonitrile (300 mL) and water (30 mL) was added Selectfluor (76 g, 214 mmol) at room temperature. The reaction mixture was stirred at 65 °C for 48 h. The reaction mass was partitioned between water and EtOAc, the organic layer was washed with water and brine, dried over Na₂SO₄ and concentrated to afford 3-fluoro-4-methyl-5-nitropyridin-2(1H)-one (32.1 g, 121 mmol, 62% yield) as a gummy solid. LCMS retention time 2.075 min [D]. MS m/z: 171.0 [M-H]⁺.
Intermediate 3B: 2-chloro-3-fluoro-4-methyl-5-nitropyridine
• 
• 2-chloro-3-fluoro-4-methyl-5-nitropyridine (8 g, 42.0 mmol, 70% yield) was prepared according to the general procedure described in Intermediate 1B using 3-fluoro-4-methyl-5-nitropyridin-2-ol (19.1, 59.9 mmol) as the starting intermediate. LCMS retention time 2.399 min [D]. MS m/z: 189.1 [M-H]⁺.
Intermediate 3C: (E)-2-(2-chloro-3-fluoro-5-nitropyridin-4-yl)-N,N-dimethylethen-1-amine
• 
• (E)-2-(2-chloro-3-fluoro-5-nitropyridin-4-yl)-N,N-dimethylethenamine (6.5 g, 26.5 mmol, 70.0 % yield) was prepared according to the general procedure described in Intermediate 1C using 2-chloro-3-fluoro-4-methyl-5-nitropyridine (7.2 g, 37.8 mmol) as the starting intermediate. LCMS retention time 2.634 min [D]. MS m/z: 246.0 [M+H]⁺.
Intermediate 3D: 5-chloro-4-fluoro-1H-pyrrolo[2,3-c]pyridine
• 
• 5-chloro-4-fluoro-1H-pyrrolo[2,3-c]pyridine (4.8 g, 28.1 mmol, 93% yield) was prepared according to the general procedure described in Intermediate 1D using (E)-2-(2-chloro-3-fluoro-5-nitropyridin-4-yl)-N,N-dimethylethenamine (7.4 g, 30.1 mmol) as the starting intermediate. LCMS retention time 1.658 min [D]. MS m/z: 171.0 [M+H]⁺.
Intermediate 3E: tert-butyl 4-(4-fluoro-1H-pyrrolo[2,3-c]pyridin-5-yl)-3,6-dihydropyridine -1(2H)-carboxylate
• 
• tert-butyl 4-(4-fluoro-1H-pyrrolo[2,3-c]pyridin-5-yl)-5,6-dihydropyridine-1(2H)-carboxylate (6.1 g, 19.22 mmol, 72.9 % yield) was prepared according to the general procedure described in Intermediate 1F using 5-chloro-4-fluoro-1H-pyrrolo[2,3-c]pyridine (4.5 g, 26.4 mmol) as the starting intermediate. LCMS retention time 2.582 min [D]. MS m/z: 318.2 [M+H]⁺.
Intermediate 3F: tert-butyl 4-(4-fluoro-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidine-1-carboxylate
• 
• tert-butyl 4-(4-fluoro-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidine-1-carboxylate (5.75 g, 18.00 mmol, 94% yield) was prepared according to the general procedure described in Intermediate 1G using tert-butyl 4-(4-fluoro-1H-pyrrolo[2,3-c]pyridin-5-yl)-5,6-dihydropyridine-1(2H)-carboxylate (6.1 g, 19.22 mmol) as the starting intermediate. LCMS retention time 2.647 min [D]. MS m/z: 320.2 [M+H]⁺.
Intermediate 3G: tert-butyl 4-(3-bromo-4-fluoro-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidine-1 -carboxylate
• 
• tert-butyl 4-(3-bromo-4-fluoro-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidine-1-carboxylate (7.1 g, 17.83 mmol, 99 % yield) was prepared according to the general procedure described in Intermediate 1H using tert-butyl 4-(4-fluoro-1H-pyrrolo[2,3-c] pyridin-5-yl)piperidine-1-carboxylate (5.75 g, 18.00 mmol) as the starting intermediate. LCMS retention time 3.067 min [D]. MS m/z: 400.2 [M+2H]⁺.
Intermediate 3H: tert-butyl 3-bromo-5-(1-(tert-butoxycarbonyl)piperidin-4-yl)-4-fluoro-1H-pyrrolo[2,3-c]pyridine-1-carboxylate
• 
• tert-butyl 3-bromo-5-(1-(tert-butoxycarbonyl)piperidin-4-yl)-4-fluoro-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (6.7 g, 13.44 mmol, 75% yield) was prepared according to the general procedure described in Intermediate 1I using tert-butyl 4-(3-bromo-4-fluoro-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidine-1-carboxylate (7.1 g, 17.83 mmol) as the starting intermediate. LCMS retention time 1.894 min [D]. MS m/z: 500.0 [M+2H]⁺.
Intermediate 3I: tert-butyl 5-(1-(tert-butoxycarbonyl)piperidin-4-yl)-4-fluoro-3-(prop-1-en-2-yl)-1H-pyrrolo[2,3-c]pyridine-1-carboxylate
• 
• tert-butyl 5-(1-(tert-butoxycarbonyl)piperidin-4-yl)-4-fluoro-3-(prop-1-en-2-yl)-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (5.7 g, 12.40 mmol, 92% yield) was prepared according to the general procedure described in Intermediate 1J using tert-butyl 3-bromo-5-(1-(tert-butoxycarbonyl)piperidin-4-yl)-4-fluoro-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (6.7 g, 13.44 mmol) as the starting intermediate. LCMS retention time 4.576 min [D]. MS m/z: 460.2 [M+H]⁺.
Intermediate 3J: tert-butyl 5-(1-(tert-butoxycarbonyl)piperidin-4-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridine-1-carboxylate
• 
• tert-butyl 5-(1-(tert-butoxycarbonyl)piperidin-4-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (4.6 g, 9.97 mmol, 80% yield) was prepared according to the general procedure described in Intermediate 1K using tert-butyl 5-(1-(tert-butoxycarbonyl)piperidin-4-yl)-4-fluoro-3-(prop-1-en-2-yl)-1H-pyrrolo[2,3-c] pyridine-1-carboxylate (5.7 g, 12.40 mmol) as the starting intermediate. LCMS retention time 1.602 min [D]. MS m/z: 462.2 [M+H]⁺.
Intermediate 3K: tert-butyl 5-(1-(tert-butoxycarbonyl)piperidin-4-yl)-4-fluoro-3-isopropyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-c]pyridine-1-carboxylate
• 
• tert-butyl 5-(1-(tert-butoxycarbonyl)piperidin-4-yl)-4-fluoro-3-isopropyl-2-(4,4, 5, 5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (2.42 g, 3.87 mmol, 74.5 % yield) was prepared according to the general procedure described in Intermediate 1L using tert-butyl 5-(1-(tert-butoxycarbonyl)piperidin-4-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (2.4 g, 5.20 mmol) as the starting intermediate. LCMS retention time 2.358 min [D]. MS m/z: 588.2 [M+H]⁺.
Intermediate 3L: tert-butyl 5-(1-(tert-butoxycarbonyl)piperidin-4-yl)-4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridine-1-carboxylate
• 
• tert-butyl 5-(1-(tert-butoxycarbonyl)piperidin-4-yl)-4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4] triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (0.42 g, 0.661 mmol, 48.5 % yield) was prepared according to the general procedure described in Intermediate 1M using tert-butyl 5-(1-(tert-butoxycarbonyl)piperidin-4-yl)-4-fluoro-3-isopropyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-c] pyridine-1-carboxylate (0.8 g, 1.362 mmol) as the starting intermediate. LCMS retention time 3.396 min [D]. MS m/z: 609.3 [M+H]⁺.
Example 3:
• 6-(4-fluoro-3-isopropyl-5-(piperidin-4-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4] triazolo[1,5-a]pyridine (0.26 g, 0.637 mmol, 92% yield) was prepared according to the general procedure described in Example 1 using tert-butyl 5-(1-(tert-butoxycarbonyl)piperidin-4-yl)-4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a] pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (0.42 g, 0.690 mmol) as the starting intermediate. LCMS retention time 1.086 min [P]. MS m/z: 409.3 [M+H]⁺; ¹H NMR (400 MHz, DMSO-d ₆) δ ppm 12.01 (bs, 1 H) 8.69 (d, J=1.0 Hz, 1H), 8.56 (d, J=2.4 Hz, 1H), 8.55 (s, 1H), 7.17 (s, 1H), 4.07 (s, 3H), 3.19-3.09 (m, 3H), 2.78 (t, J=11.2 Hz, 2H), 1.92 (d, J=8.8 Hz, 2H), 1.86 (s, 3H), 1.72 (d, J=12.7 Hz, 2H), 1.35 (d, J=6.8 Hz, 6H).
EXAMPLE 4 6-(3-isopropyl-5-(piperidin-4-yl)-1h-pyrrolo[2,3-c]pyridin-2-yl)-8-methyl-[1,2,4]triazolo [1,5-a]pyridine
• 
Intermediate 4A: tert-butyl 4-(1H-pyrrolo[2,3-c]pyridin-5-yl)-5,6-dihydropyridine-1(2H)-carboxylate
• 
• To a solution of 5-bromo-1H-pyrrolo[2,3-c]pyridine (3.2 g, 16.24 mmol) in dioxane (60 mL) and water (20.00 mL) solvent mixture were added tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate(5.02 g, 16.24 mmol) and potassium phosphate tribasic (10.34 g, 48.7 mmol). The reaction mixture was degassed with nitrogen for 5 min., PdCl₂(dppf)-CH₂Cl₂ adduct (1.326 g, 1.624 mmol) was added, and the reaction mixture was stirred in a sealed tube at 90 °C for 3 h. The reaction mass was concentrated, then the residue was diluted with EtOAc (20 mL), the solids were filtered, the filtrate was collected and concentrated to get crude compound. The crude compound was purified by silica gel chromatography on an ISCO instrument using 40 g silica column, the compound was eluted in 15% EA in hexanes, the fractions were collected and concentrated to afford tert-butyl 4-(1H-pyrrolo[2,3-c] pyridin-5-yl)-5,6-dihydropyridine-1(2H)-carboxylate (2.5 g, 8.35 mmol, 51% yield) as a pale brown solid. LCMS retention time 0.95 min [L] MS m/z: 300.2 [M+H]⁺.
Intermediate 4B: tert-butyl 4-(1H-pyrrolo[2,3-c]pyridin-5-yl)piperidine-1-carboxylate
• 
• To a solution of tert-butyl 4-(1H-pyrrolo[2,3-c]pyridin-5-yl)-5,6-dihydropyridine-1(2H)-carboxylate (3.2 g, 10.69 mmol) in MeOH (20 mL) and EtOAc (20 mL) solvent mixture was added Pd/C (1.138 g, 10.69 mmol). The reaction mixture was stirred at room temperature for 3 h under hydrogen. The reaction mass was filtered through celite, washed with EtOAc (2 X 50 mL) and concentrated to afford tert-butyl 4-(1H-pyrrolo[2,3-c]pyridin-5-yl)piperidine-1-carboxylate (2.5 g, 8.30 mmol, 78 % yield) as an off-white solid. LCMS retention time 0.88min [D] MS m/z: 302.2 [M+H]⁺.
Intermediate 4C: tert-butyl 4-(3-bromo-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidine-1-carboxylate
• 
• To a solution of tert-butyl 4-(1H-pyrrolo[2,3-c]pyridin-5-yl)piperidine-1-carboxylate (300 mg, 0.995 mmol) in DMF (5 mL) was added NBS (142 mg, 0.796 mmol) at 0 °C. The reaction mixture was stirred at same temperature for 1 h. The reaction was quenched with ice (50 g). The reaction mixture was extracted with EtOAc (3 X 50 mL), the combined organic layer was concentrated to get crude compound. The crude was purified by silica gel chromatography on an ISCO instrument using 24 g silica column, the compound was eluted in 10% EA in hexanes, the fractions were collected and concentrated to afford tert-butyl 4-(3-bromo-1H-pyrrolo[2,3-c]pyridin-5-yl) piperidine-1-carboxylate (300 mg, 0.789 mmol, 79 % yield) as an off-white solid. LCMS retention time 1.31min [G] MS m/z: 382.1 [M+2H]⁺.
Intermediate 4D: tert-butyl 4-(3-(prop-1-en-2-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidine-1 -carboxylate
• 
• tert-butyl 3-(3-isopropyl-1H-indol-5-yl)azetidine-1-carboxylate (700 mg, 1.759 mmol, 33.4 % yield) was prepared according to the general procedure described in Intermediate 4A using tert-butyl 4-(3-bromo-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidine-1-carboxylate (2.5 g, 6.57 mmol) as the starting intermediate. LCMS retention time 0.51 min [D] MS m/z: 340.8 [M+H]⁺.
Intermediate 4E: tert-butyl4-(3-isopropyl-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidine-1-carboxylate
• 
• tert-butyl 4-(3-isopropyl-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidine-1-carboxylate (1.8 g, 2.52 mmol, 48% yield) was prepared according to the general procedure described in Intermediate 4B using tert-butyl 4-(3-(prop-1-en-2-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl) piperidine-1-carboxylate (1.9 g, 5.56 mmol) as the starting intermediate. LCMS retention time 0.80 min [D]. MS m/z: 344.2 [M+H]⁺.
Intermediate 4F: tert-butyl 5-(1-(tert-butoxycarbonyl)piperidin-4-yl)-3-isopropyl-1H-pyrrolo[2,3-c]pyridine-1-carboxylate
• 
• To a solution of tert-butyl 4-(3-isopropyl-1H-pyrrolo[2,3-c]pyridin-5-yl) piperidine-1-carboxylate (1.9 g, 5.53 mmol) in DCM (10 mL) were added Boc₂O (1.670 mL, 7.19 mmol) and DMAP (10.14 g, 83 mmol) at room temperature. The reaction mixture was stirred at same temperature for 12 h. The reaction mass was concentrated to get crude compound. The crude compound was purified by silica gel chromatography on an ISCO instrument using 12 g silica column, the compound was eluted in 35% EA in hexanes, the fractions were collected and concentrated to afford tert-butyl 5-(1-(tert-butoxycarbonyl)piperidin-4-yl)-3-isopropyl-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (1.2 g, 2.71 mmol, 49 % yield) as an off-white solid. LCMS retention time 1.99 min [D] MS m/z: 444.4 [M+H]⁺.
Intermediate 4G: tert-butyl 5-(1-(tert-butoxycarbonyl)piperidin-4-yl)-3-isopropyl-2-(4,4, 5, 5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-c]pyridine-1-carboxylate
• 
• To a solution of tert-butyl 5-(1-(tert-butoxycarbonyl)piperidin-4-yl)-3-isopropyl-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (550 mg, 1.240 mmol) in THF (3 mL) was added LDA (2.480 mL, 4.96 mmol) at -78 °C. The reaction mixture was stirred at the same temperature for 1.5 h. Next, 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.769 mL, 3.72 mmol) was added and the reaction mixture was stirred at -45 °C for 2 h. The reaction was quenched with ammonia chloride (20 mL). The reaction mixture was separated, the organic layers were concentrated to get crude compound. The crude compound was purified by silica gel chromatography on an ISCO instrument using 24 g silica column, the compound was eluted in 25% EA in hexanes, the fractions were collected and concentrated to afford tert-butyl 5-(1-(tert-butoxycarbonyl)piperidin-4-yl)-3-isopropyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (320 mg, 0.562 mmol, 45% yield). LCMS retention time 1.03 min [D]. MS m/z: 514.4 [M+H-tBu]⁺.
Intermediate 4H: tert-butyl5-(1-(tert-butoxycarbonyl)piperidin-4-yl)-3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridine-1-carboxylate
• 
• To a solution of tert-butyl 5-(1-(tert-butoxycarbonyl)piperidin-4-yl)-3-isopropyl-2-(4,4, 5, 5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (300 mg, 0.527 mmol) in dioxane (18 mL) and water (6.00 mL) solvent mixture were added 6-bromo-8-methyl-[1,2,4]triazolo[1,5-a]pyridine (335 mg, 1.580 mmol) and potassium phosphate tribasic (335 mg, 1.580 mmol). The reaction mixture was degassed with nitrogen for 5 min, potassium phosphate tribasic (335 mg, 1.580 mmol) was added, and the reaction mixture was stirred in a sealed tube at 90 °C for 3 h. The reaction mass was concentrated, the residue was dissolved in EtOAc (50 mL), the solid was filtered and washed with EtOAc (2 X 30 mL), the combined filtrates were collected and concentrated to get crude compound. The crude compound was purified by silica gel chromatography on an ISCO instrument using 24 g silica column, the compound was eluted in 35% EA in hexanes, the fractions were collected and concentrated to afford tert-butyl 5-(1-(tert-butoxycarbonyl)piperidin-4-yl)-3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (150 mg, 0.261 mmol, 49.5 % yield) as an off-white solid. LCMS retention time 1.16 min [D] MS m/z: 575.3 [M+H]⁺.
Example 4:
• To a solution of tert-butyl 5-(1-(tert-butoxycarbonyl)piperidin-4-yl)-3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (31 mg, 0.054 mmol) in DCM (2 mL) was added 4 M HCl in dioxane (1 mL, 4.00 mmol). The mixture was stirred at room temperature for 3 h. The reaction mass was concentrated and the residue was triturated with diethyl ether (2 X 10 mL), and dried under vacuum to afford 6-(3-isopropyl-5-(piperidin-4-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methyl-[1,2,4] triazolo[1,5-a]pyridine (2.1 mg, 5.61 µmol, 10% yield) as a white solid. LCMS retention time 1.209 min [G], MS m/z: 375.2 [M+H]⁺; ¹H NMR (400 MHz, METHANOL-d ₄) δ ppm 8.85 (s, 1 H), 8.69 (s, 1 H), 8.52 (s, 1 H), 7.70 (s, 2 H), 3.44-3.61 (m, 3 H), 3.38 (br. s., 1 H), 3.05-3.27 (m, 3 H), 2.75 (s, 3 H), 2.03-2.27 (m, 4 H), 1.94 (s, 3 H), 1.53 (d, J=6.85 Hz, 5 H).
EXAMPLE 5 2-(dimethylamino)-1-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a] pyridine-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidin-1-yl)ethan-1-one
• 
• To a solution of 6-(3-isopropyl-5-(piperidin-4-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine (25 mg, 0.067 mmol) in DMF (1 mL) were added triethylamine (0.028 mL, 0.200 mmol), 2-(dimethylamino)acetic acid (13.77 mg, 0.134 mmol) and HATU (76 mg, 0.200 mmol) at 0 °C. The reaction mixture was stirred at room temperature for 3 h. The reaction mass was purified by preparative LCMS method D2, the fractions containing the product were combined and dried using Genevac centrifugal evaporator to afford 2-(dimethylamino)-1-(4-(3-isopropyl-2-(8-methyl-[1,2,4] triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl) piperidin-1-yl)ethanone (11 mg, 0.024 mmol, 35.9 % yield) as a pale solid. LCMS retention time 1.346 min [E]. MS m/z: 460.3 [M+H]⁺; ¹H NMR (400 MHz, DMSO-d ₆) δ ppm 11.62 (s, 1 H), 8.90 (s, 1 H), 8.65 (s, 1 H), 8.55 (s, 1 H), 7.62 (s, 1 H), 7.53 (s, 1 H), 4.52-4.48 (m, 1 H), 4.16-4.11 (m, 1 H), 3.26-3.12 (m, 3 H), 3.04-2.96 (m, 2 H), 2.67-2.64 (m, 1 H), 2.63 (s 3 H), 2.25 (s, 6 H), 1.90-1.85 (m 2 H), 1.82-1.75 (m, 1 H), 1.66-1.62 (m, 1 H), 1.41 (d, J=6.85 Hz, 6 H).
EXAMPLE 6 6-(4-chloro-3-isopropyl-5-(piperazin-1-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine
• 
Intermediate 6A: tert-butyl 4-(4-methyl-5-nitropyridin-2-yl)piperazine-1-carboxylate
• 
• To a solution of 2-bromo-4-methyl-5-nitropyridine (10 g, 46.1 mmol) in acetonitrile (50 mL) were added tert-butyl piperazine-1-carboxylate (8.58 g, 46.1 mmol) and DIPEA (12.07 mL, 69.1 mmol) at room temperature. The reaction mixture was stirred at 60 °C for 4 h. The solids were filtered, washed with acetonitrile (50 mL) and dried under vacuum to afford tert-butyl 4-(4-methyl-5-nitropyridin-2-yl)piperazine-1-carboxylate (10 g, 19.85 mmol, 43% yield) as a white solid. LCMS retention time 1.39 min [G], MS m/z: 323.5 [M+H]⁺.
Intermediate 6B: tert-butyl(E)-4-(4-(2-(dimethylamino)vinyl)-5-nitropyridin-2-yl) piperazine-1 -carboxylate.
• 
• To a solution tert-butyl 4-(4-methyl-5-nitropyridin-2-yl)piperazine-1-carboxylate (24 g, 74.5 mmol) in DMF (70 mL) was added 1,1-dimethoxy-N,N-dimethylmethanamine (49.8 mL, 372 mmol). The reaction mixture was stirred at 90 °C for 24 h. The reaction mass was concentrated, the residue was dissolved in DCM (250 mL), washed with water (2 X 50 mL), brine (20 mL), dried (Na₂SO₄) and concentrated to afford (E)-tert-butyl 4-(4-(2-(dimethylamino)vinyl)-5-nitropyridin-2-yl)piperazine-1-carboxylate (12 g, 20.03 mmol, 27% yield) as an oil. LCMS retention time 1.39 min [L] MS m/z: 378.5 [M+H]⁺.
Intermediate 6C: tert-butyl(E)-4-(4-(2-(dimethylamino)vinyl)-5-nitropyridin-2-yl) piperazine-1-carboxylate
• 
• To a solution tert-butyl (E)-tert-butyl 4-(4-(2-(dimethylamino)vinyl)-5-nitropyridin-2-yl)piperazine-1-carboxylate (15 g, 39.7 mmol) in MeOH (150 mL) was added Pd/C (1.5 g, 14.10 mmol). The reaction mixture was stirred at 60 psi under hydrogen in an autoclave for 12 h. The Pd/C was filtered through celite, washed with EtOAc (2 X 50 mL), the filtrates were collected and concentrated to afford tert-butyl 4-(1H-pyrrolo[2,3-c]pyridin-5-yl)piperazine-1-carboxylate (6.5 g, 16.34 mmol, 41.1 % yield) as an off-white solid. LCMS retention time 2.10 min [L] MS m/z: 303.2 [M+H]⁺.
Intermediate 6D: tert-butyl 4-(3-bromo-1H-pyrrolo[2,3-c]pyridin-5-yl)piperazine-1-carboxylate
• 
• tert-butyl 4-(3-bromo-1H-pyrrolo[2,3-c]pyridin-5-yl)piperazine-1-carboxylate (6.5 g, 15.00 mmol, 76 % yield) was prepared according to the general procedure described in Intermediate 4C using tert-butyl 4-(1H-pyrrolo[2,3-c]pyridin-5-yl) piperazine-1-carboxylate (6 g, 19.84 mmol) as the starting intermediate. LCMS retention time 0.98 min [G]. MS m/z: 382.9 [M+H]⁺.
Intermediate 6E: tert-butyl 3-bromo-5-(4-(tert-butoxycarbonyl)piperazin-1-yl)-1H-pyrrolo[2,3-c]pyridine-1-carboxylate
• 
• To a solution of tert-butyl 4-(3-bromo-1H-pyrrolo[2,3-c]pyridin-5-yl)piperazine-1-carboxylate (1.1 g, 2.89 mmol) in THF (20 mL) were added triethylamine (1.206 mL, 8.66 mmol), Boc₂O (0.804 mL, 3.46 mmol) and DMAP (7.05 mg, 0.058 mmol) at room temperature. The reaction mixture was stirred at same temperature for 12 h. The reaction mass was concentrated to get the crude compound. The crude compound was purified by silica gel chromatography on an ISCO instrument using 24 g silica column, the compound was eluted in 35% EA in hexanes, the fractions were collected and concentrated to afford tert-butyl 3-bromo-5-(4-(tert-butoxycarbonyl)piperazin-1-yl)-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (900 mg, 1.458 mmol, 50% yield) as a gummy solid. LCMS retention time 1.88 min [G] MS m/z: 483.3 [M+H]⁺.
Intermediate 6F: tert-butyl 5-(4-(tert-butoxycarbonyl)piperazin-1-yl)-3-(prop-1-en-2-yl)-1H-pyrrolo[2,3-c]pyridine-1-carboxylate.
• 
• tert-butyl 5-(4-(tert-butoxycarbonyl)piperazin-1-yl)-3-(prop-1-en-2-yl)-1H-pyrrolo[2,3-c] pyridine-1-carboxylate (450 mg, 0.590 mmol, 29% yield) was prepared according to the general procedure described in Intermediate 4D using tert-butyl 5-(4-(tert-butoxycarbonyl)piperazin-1-yl)-3-isopropyl-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (900 mg, 2.024 mmol) as the starting intermediate. LCMS retention time 1.88 min [L] MS m/z: 443.5 [M+H]⁺.
Intermediate 6G: tert-butyl 5-(4-(tert-butoxycarbonyl)piperazin-1-yl)-3-isopropyl-1H-pyrrolo[2,3-c]pyridine-1-carboxylate
• 
• tert-butyl 5-(4-(tert-butoxycarbonyl)piperazin-1-yl)-3-isopropyl-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (310 mg, 0.572 mmol, 56% yield) was prepared according to the general procedure described in Intermediate 4E using tert-butyl 5-(4-(tert-butoxycarbonyl)piperazin-1-yl)-3-(prop-1-en-2-yl)-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (450 mg, 1.017 mmol) as the starting intermediate. LCMS retention time 1.92 min [L] MS m/z: 445.5 [M+H]⁺.
Intermediate 6H: tert-butyl5-(4-(tert-butoxycarbonyl)piperazin-1-yl)-4-chloro-3-isopropyl-1H-pyrrolo[2,3-c]pyridine-1-carboxylate
• 
• To a solution of tert-butyl 5-(4-(tert-butoxycarbonyl)piperazin-1-yl)-3-isopropyl-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (1 g, 2.249 mmol) in DCE (10 mL) was added NCS (0.751 g, 5.62 mmol) at room temperature. The reaction mixture was stirred at room temperature for 12 h. The reaction was quenched with water. The reaction mixture was extracted with DCM, the organic layer was concentrated to get crude compound. The crude compound was purified by silica gel chromatography on an ISCO instrument using 24 g silica column, the compound was eluted in 20% EA in hexanes, the fractions were collected and concentrated to afford tert-butyl 5-(4-(tert-butoxycarbonyl)piperazin-1-yl)-4-chloro-3-isopropyl-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (150 mg, 0.307 mmol, 13% yield) as an off-white solid. LCMS retention time 3.487 min [G], MS m/z: 479.2 [M+H]⁺.
Intermediate 6I: tert-butyl 5-(4-(tert-butoxycarbonyl)piperazin-1-yl)-4-chloro-3-isopropyl-2-(4,4, 5, 5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-c]pyridine-1-carboxylate
• 
• tert-butyl 5-(4-(tert-butoxycarbonyl)piperazin-1-yl)-4-chloro-3-isopropyl-2-(4,4, 5, 5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (158 mg, 0.243 mmol, 68.4 % yield) was prepared according to the general procedure described in Intermediate 1L using tert-butyl 5-(4-(tert-butoxycarbonyl)piperazin-1-yl)-4-chloro-3-isopropyl-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (170 mg, 0.355 mmol) as the starting intermediate. LCMS retention time 3.328 min [G], MS m/z: 605.4 [M+H]⁺.
Intermediate 6J: tert-butyl 5-(4-(tert-butoxycarbonyl)piperazin-1-yl)-4-chloro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridine-1-carboxylate
• 
• tert-butyl 5-(4-(tert-butoxycarbonyl)piperazin-1-yl)-4-chloro-3-isopropyl-2-(8-methoxy-[1,2,4] triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (180 mg, 0.207 mmol, 62.6 % yield) was prepared according to the general procedure described in Intermediate 1M using tert-butyl 5-(4-(tert-butoxycarbonyl)piperazin-1-yl)-4-chloro-3-isopropyl-2-(4,4,5,5-tetramethyl-15-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-c] pyridine-1-carboxylate (200 mg, 0.331 mmol) as the starting intermediate. LCMS retention time 1.96 min [D], MS m/z: 628.2 [M+H]⁺.
Example 6:
• 6-(4-chloro-3-isopropyl-5-(piperazin-1-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4] triazolo[1,5-a]pyridine (140 mg, 0.329 mmol, 86 % yield) was prepared according to the general procedure described in Example 4 using tert-butyl 5-(4-(tert-butoxycarbonyl)piperazin-1-yl)-4-chloro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (240 mg, 0.383 mmol) in HCl (3 mL, 12.00 mmol) as the starting intermediate. LCMS retention time 1.329 min [E], MS m/z: 426.2 [M+H]⁺; ¹H NMR (400 MHz, DMSO-d₆) δ ppm 8.71 (d, J=1.2 Hz, 1H), 8.54 (s, 1H), 8.45 (s, 1H), 7.15 (s, 1H), 4.04 (s, 3H), 3.06 (d, J=5.1 Hz, 4H), 2.99-2.91 (m, 4H), 1.87 (s, 2H), 1.33 (d, J=7.3 Hz, 6H).
EXAMPLE 7 6-(3-isopropyl-5-(piperazin-1-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo [1,5-a]pyridine
• 
Intermediate 7A: tert-butyl5-(4-(tert-butoxycarbonyl)piperazin-1-yl)-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridine-1-carboxylate
• 
• To a solution of tert-butyl 5-(4-(tert-butoxycarbonyl)piperazin-1-yl)-4-chloro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (100 mg, 0.160 mmol) in MeOH (5 mL) was added Pd/C (17.00 mg, 0.160 mmol). The mixture was stirred at room temperature under hydrogen bladder for 3 h. The reaction mass was filtered, washed with EtOAc (2 × 50 mL) and concentrated to afford tert-butyl 5-(4-(tert-butoxycarbonyl)piperazin-1-yl)-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (65 mg, 0.019 mmol, 11% yield) as a pale solid. LCMS retention time 1.64 min [D] MS m/z: 592.6 [M+H]⁺.
Example 7:
• 6-(3-isopropyl-5-(piperazin-1-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (0.7 mg, 1.788 µmol, 2% yield) was prepared according to the general procedure described in Example 4 using tert-butyl 5-(4-(tert-butoxycarbonyl) piperazin-1-yl)-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo [1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (65 mg, 0.110 mmol) as the starting intermediate. LCMS retention time 1.18 min [F], MS m/z: 392.1 [M+H]⁺; ¹H NMR (400MHz, DMSO-d₆) δ ppm 11.30 (s, 1H), 8.64 (s, 1H), 8.53 (s, 1H), 8.42 (s, 1H), 7.17 (s, 1H), 6.90 (s, 1H), 4.07 (s, 3H), 2.90 (br. s., 4H), 1.90 (s, 2H), 1.42 (d, J=7.1 Hz, 6H).
EXAMPLE 42 1-(4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-(oxetan-3-yl)piperidin-4-amine
• 
Intermediate 42A: 8-(4-fluoro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-1,4-dioxa-8-azaspiro[4.5]decane
• 
• 8-(4-fluoro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-1,4-dioxa-8-azaspiro[4.5]decane (3.7 g, 9.08 mmol, 68.3 % yield) was prepared as described in the preparation of Intermediate 213B using 5-chloro-4-fluoro-1-((2-(trimethylsilyl)ethoxy) methyl)-1H-pyrrolo[2,3-c]pyridine (4.0 g, 13.30 mmol) and 1,4-dioxa-8-azaspiro[4.5]decane (2.86 g, 19.94 mmol) as the starting intermediates. LCMS retention time 3.410 min [D]. MS (E^-) m/z: 408.2 (M+H).
Intermediate 42B: 8-(3-bromo-4-fluoro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-1,4-dioxa-8-azaspiro[4.5]decane
• 
• 8-(3-bromo-4-fluoro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-1,4-dioxa-8-azaspiro[4.5]decane (5.01 g, 10.30 mmol, 87 % yield) was prepared as described in the preparation of Intermediate 213C using 8-(4-fluoro-1-((2-(trimethylsilyl)ethoxy) methyl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-1,4-dioxa-8-azaspiro[4.5]decane (4.8 g, 11.78 mmol) as the starting intermediate. LCMS retention time 1.77 min [L]. MS (E^-) m/z: 488.8 (M+2H).
Intermediate 42C: 8-(4-fluoro-3-(prop-1-en-2-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-1,4-dioxa-8-azaspiro[4.5]decane
• 
• 8-(4-fluoro-3-(prop-1-en-2-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-1,4-dioxa-8-azaspiro[4.5]decane (3.8 g, 8.49 mmol, 82 % yield) was prepared as described in the preparation of intermediate 213D using 8-(3-bromo-4-fluoro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-1,4-dioxa-8-azaspiro[4.5]decane (5.01 g, 10.30 mmol) and 4,4,5,5-tetramethyl-2-(prop-1-en-2-yl)-1,3,2-dioxaborolane (2.077 g, 12.36 mmol) as the starting intermediates. LCMS retention time 4.033 min [D]. MS (E-) m/z: 448.2 (M+H).
Intermediate 42D: 8-(4-fluoro-3-isopropyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-1,4-dioxa-8-azaspiro[4.5]decane
• 
• 8-(4-fluoro-3-isopropyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-c] pyridin-5-yl)-1,4-dioxa-8-azaspiro[4.5]decane (3.6 g, 8.01 mmol, 97 % yield) was prepared as described in the preparation of Intermediate 213E using 8-(4-fluoro-3-(prop-1-en-2-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-1,4-dioxa-8-azaspiro[4.5]decane (3.7 g, 8.27 mmol) as the starting intermediate. LCMS retention time 4.193 min [D]. MS (E^-) m/z: 450.2 (M+H).
Intermediate 42E: 8-(4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-5-yl)-1,4-dioxa-8-azaspiro[4.5]decane
• 
• 8-(4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-5-yl)-1,4-dioxa-8-azaspiro[4.5]decane (1.4 g, 4.38 mmol, 79 % yield) was prepared as described in the preparation of Intermediate 213F using 8-(4-fluoro-3-isopropyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-1,4-dioxa-8-azaspiro[4.5]decane (2.5 g, 5.56 mmol) as the starting intermediate. LCMS retention time 2.709 min [D]. MS (E^-) m/z: 320.2 (M+H).
Intermediate 42F: tert-butyl 4-fluoro-3-isopropyl-5-(1,4-dioxa-8-azaspiro[4.5]decan-8-yl)-1H-pyrrolo[2,3-c]pyridine-1-carboxylate
• 
• tert-butyl 4-fluoro-3-isopropyl-5-(1,4-dioxa-8-azaspiro[4.5]decan-8-yl)-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (1.41 g, 3.36 mmol, 89 % yield) was prepared as described in the preparation of Intermediate 213G using 8-(4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-5-yl)-1,4-dioxa-8-azaspiro[4.5]decane (1.2 g, 3.76 mmol) as the starting intermediate. LCMS retention time 4.227 min [D]. MS (E^-) m/z: 420.2 (M+H).
Intermediate 42G: tert-butyl 4-fluoro-3-isopropyl-5-(1,4-dioxa-8-azaspiro[4.5]decan-8-yl)-2-(4,4, 5, 5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-c]pyridine-1-carboxylate
• 
• tert-butyl 4-fluoro-3-isopropyl-5-(1,4-dioxa-8-azaspiro[4.5]decan-8-yl)-2-(4,4, 5, 5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (1.26 g, 2.310 mmol, 69.2 % yield) was prepared as described in the preparation of Intermediate 213H using tert-butyl 4-fluoro-3-isopropyl-5-(1,4-dioxa-8-azaspiro[4.5]decan-8-yl)-1H-pyrrolo[2,3-c] pyridine-1-carboxylate (1.4 g, 3.34 mmol) as the starting intermediate. LCMS retention time 4.527 min [D]. MS (E^-) m/z: 546.3 (M+H).
Intermediate 42H: tert-butyl 4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-(1,4-dioxa-8-azaspiro[4.5]decan-8-yl)-1H-pyrrolo[2,3-c]pyridine-1-carboxylate
• 
• tert-butyl 4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-(1,4-dioxa-8-azaspiro[4.5]decan-8-yl)-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (0.51 g, 0.900 mmol, 78 % yield) was prepared as described in the preparation of Intermediate 2131 using tert-butyl 4-fluoro-3-isopropyl-5-(1,4-dioxa-8-azaspiro[4.5]decan-8-yl)-2-(4,4, 5, 5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (0.63 g, 1.155 mmol) and 6-bromo-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (0.342 g, 1.501 mmol) as the starting intermediates. LCMS retention time 3.460 min [D]. MS (E^-) m/z: 567.5 (M+H).
Intermediate 42I: 1-(4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidin-4-one
• 
• 1-(4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidin-4-one (0.32 g, 0.757 mmol, 95 % yield) was prepared as described in the preparation of Example 4 using tert-butyl 4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-(1,4-dioxa-8-azaspiro[4.5]decan-8-yl)-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (0.45 g, 0.794 mmol) as the starting intermediate. LCMS retention time 2.129 min [D]. MS (E^-) m/z: 423.2 (M+H).
Example 42:
• To a solution of 1-(4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a] pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidin-4-one (25 mg, 0.059 mmol) and oxetan-3-amine (6.49 mg, 0.089 mmol) in mixture of DMF (0.5 mL) and THF (0.5 mL) was added AcOH (0.339 µl, 5.92 µmοl). The reaction mixture was stirred for 12 h at ambient temperature. Sodium cyanoborohydride (7.44 mg, 0.118 mmol) was added, and the reaction mixture was stirred for 1 h at ambient temperature. The reaction was quenched with 0.2 ml of water. The reaction mixture was concentrated to get crude compound. The crude material was purified by Preparative LCMS using method D2, fractions containing the product was combined and dried using Genevac centrifugal evaporator to afford 1-(4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-(oxetan-3-yl)piperidin-4-amine (16.6 mg, 0.034 mmol, 57.0 % yield). LCMS retention time 1.383 min [P]. MS m/z: 480.3 [M+H] ⁺; ¹H NMR (400MHz, DMSO-d₆) δ 11.77 (s, 1H), 8.67 (s, 1H), 8.54 (s, 1H), 8.29 (s, 1H), 7.15 (s, 1H), 4.66 (t, J=6.6 Hz, 2H), 4.36 (t, J=6.2 Hz, 2H), 4.06 (s, 4H), 3.26 (br. s., 2H), 3.17 (s, 1H), 2.80 (t, J=11.9 Hz, 2H), 1.91 (s, 2H), 1.79 (d, J=13.9 Hz, 2H), 1.50-1.38 (m, 2H), 1.34 (d, J=7.1 Hz, 6H).
EXAMPLE 213 6-(3-isopropyl-4-methyl-5-(piperazin-1-yl)-1H-pyrrolo [2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine
• 
Intermediate (213A):5-chloro-4-methyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-c]pyridine
• 
• To a solution of 5-chloro-4-methyl-1H-pyrrolo[2,3-c]pyridine (5.6 g, 33.6 mmol) in dry THF (120 mL) was added sodium hydride (1.266 g, 52.8 mmol) portion wise at 0 °C, then stirred for 30 mins, then SEM-Cl (7.49 mL, 42.2 mmol) was added to the reaction mixture at 0 °C. The reaction was continued for 4 hrs at ambient temperature. The reaction was quenched with aqueous NH₄Cl solution. The mixture was partitioned between water and EtOAc. Combined organic layers were washed with water, brine solution, dried over Na₂SO₄ and concentrated, then purified over silica gel eluting 40% EA/hexane to get 5-chloro-4-methyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-c]pyridine (8.9 g, 30.0 mmol, 89 % yield). LCMS retention time 3.500 min [D]. MS (E^-) m/z: 297.3 (M+H).
Intermediate 213B: tert-butyl 4-(4-methyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperazine-1-carboxylate
• 
• A solution of 5-chloro-4-methyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-c]pyridine (5g, 16.84 mmol) and tert-butyl piperazine-1-carboxylate (3.76 g, 20.21 mmol) in 1,4-Dioxane (60 mL) was purged with nitrogen for 5 mins, then chloro(2-dicyclohexylphosphino-2',6'-diisopropoxy-1,1 '-biphenyl)[2-(2'-amino-1,1'-biphenyl)]palladium(II) (0.680 g, 0.875 mmol) was added. The reaction mixture was again purged for 2 min and heated in a sealed tube at 110 °C for 3 h. The reaction mixture was filtered through Celite and was diluted with EtOAc (50 mL), washed with water (30 mL), brine (10 mL), dried (Na₂SO₄) and concentrated to get crude material. The crude material was purified by silica gel chromatography on an ISCO instrument using 24 g silica column, the compound was eluted in 30% EtOAc in hexanes, the fractions were collected and concentrated to afford tert-butyl 4-(4-methyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperazine-1-carboxylate (5.1 g, 11.42 mmol, 67.8 % yield). LCMS retention time 1.46 min [L]. MS (E^-) m/z: 447.3 (M+H).
Intermediate 213C: tert-butyl 4-(3-bromo-4-methyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperazine-1-carboxylate
• 
• To a solution of tert-butyl 4-(4-methyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperazine-1-carboxylate (3.6 g, 8.06 mmol) in DMF (60 mL) at 0 °C was added a solution of NBS (1.41 g, 8.08 mmol) in DMF (20 mL). The reaction mixture was stirred for 3 h at room temperature. The reaction mixture was concentrated under vacuum and 50 mL of water was added. The mixture was extracted with EtOAc(2×100ml), combined organic layers washed with brine solution, dried over Na₂SO₄, concentrated and purified over silica gel eluting 25% EA in hexane to afford tert-butyl4-(3-bromo-4-methyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperazine-1-carboxylate (3.5 g, 6.66 mmol, 83 % yield). LCMS retention time 1.73 min [L]. MS (E^-) m/z: 527.3
Intermediate 213D: tert-butyl 4-(4-methyl-3-(prop-1-en-2-yl)-1-((2-(trimethylsilyl) ethoxy)methyl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperazine-1-carboxylate
• 
• To a solution of 4-(3-bromo-4-methyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperazine-1-carboxylate (3.4 g, 6.47 mmol) and 4,4,5,5-tetramethyl-2-(prop-1-en-2-yl)-1,3,2-dioxaborolane (3.04 g, 18.12 mmol) in mixture of THF (160 mL) and water (16 mL) was added potassium phosphate tribasic (4.12 g, 19.41 mmol). The reaction mixture was purged with nitrogen for 5 mins, then 2nd generation XPhos precatalyst (0.51 g, 0.647 mmol) was added. The reaction mixture was purged again for 2 mins. The reaction mixture was heated in a sealed tube at 60 °C for 2 h. The reaction mass was cooled and filtered through small pad of Celite. The filtrate obtained was concentrated to provide crude material. The crude material was purified by column chromatography through silica gel eluting 25% EtOAc in hexane to afford tert-butyl 4-(4-methyl-3-(prop-1-en-2-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperazine-1-carboxylate (2.6 g, 5.34 mmol, 83 % yield). LCMS retention time 1.79 min [L]. MS (E^-) m/z: 487.5 (M+H).
Intermediate 213E: tert-butyl 4-(3-isopropyl-4-methyl-1-((2-(trimethylsilyl)ethoxy) methyl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperazine-1-carboxylate
• 
• To a solution of tert-butyl 4-(4-methyl-3-(prop-1-en-2-yl)-1-((2-(trimethylsilyl) ethoxy)methyl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperazine-1-carboxylate (3.5 g, 7.19 mmol) was taken in ethyl acetate (120 mL). Pd-C (0.71 g, 7.19 mmol) was added and the reaction mixture was stirred under H₂ pressure (bladder) for 2 h. The reaction mixture was filtered through Celite, washed the Celite bed with MeOH, MeOH was concentrated under vacuum to get tert-butyl 4-(3-isopropyl-4-methyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperazine-1-carboxylate (2.3 g, 4.71 mmol, 65.4 % yield). LCMS retention time 1.83 min [L]. MS (E^-) m/z: 489.4 (M+H).
Intermediate 213F: tert-butyl 4-(3-isopropyl-4-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl) piperazine-1-carboxylate
• 
• To a solution of tert-butyl 4-(3-isopropyl-4-methyl-1-((2-(trimethylsilyl)ethoxy) methyl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperazine-1-carboxylate (2.6 g, 5.32 mmol) in DMF (30 mL) at 0 °C was added TBAF (21.28 mL, 21.28 mmol) and ethylenediamine (1.602 mL, 23.94 mmol). The reaction mixture was stirred for 6 h at 80 °C. The reaction mixture was concentrated and partitioned between water and EtOAc, the organic layer was separated and washed with water, brine solution, dried over Na₂SO₄, concentrated to get tert-butyl 4-(3-isopropyl-4-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl)piperazine-1-carboxylate (1.81 g, 5.05 mmol, 95 % yield). LCMS retention time 1.07 min [L]. MS (E^- ) m/z: 359.3 (M+H).
Intermediate 213G: tert-butyl 5-(4-(tert-butoxycarbonyl)piperazin-1-yl)-3-isopropyl-4-methyl-1H-pyrrolo[2,3-c]pyridine-1-carboxylate
• 
• To a solution of tert-butyl 5-(4-(tert-butoxycarbonyl)piperazin-1-yl)-3-isopropyl-4-methyl-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (1.5 g, 3.27 mmol, 58.6 % yield) was prepared as described in the preparation of Intermediate 11 using tert-butyl 4-(3-isopropyl-4-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl)piperazine-1-carboxylate (2 g, 5.58 mmol) as the starting intermediate. LCMS retention time 1.96 min [L]. MS (E^-) m/z: 459.5 (M+H).
Intermediate 213H: tert-butyl 5-(4-(tert-butoxycarbonyl)piperazin-1-yl)-3-isopropyl-4-methyl-2-(4,4, 5, 5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-c]pyridine-1-carboxylate
• 
• To a solution of tert-butyl 5-(4-(tert-butoxycarbonyl)piperazin-1-yl)-3-isopropyl-4-methyl-2-(4,4, 5, 5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (1.22 g, 2.087 mmol, 80 % yield) was prepared as described in the preparation of Intermediate 1L using tert-butyl 5-(4-(tert-butoxycarbonyl)piperazin-1-yl)-3-isopropyl-4-methyl-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (1.2 g, 2.62 mmol) and 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (5.34 mL, 26.2 mmol) as the starting intermediates. LCMS retention time 3.155 min [D]. MS (E^-) m/z: 585.4 (M+H).
Intermediate 2131: tert-butyl 5-(4-(tert-butoxycarbonyl)piperazin-1-yl)-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-methyl-1H-pyrrolo[2,3-c]pyridine-1-carboxylate
• 
• To a solution of tert-butyl 5-(4-(tert-butoxycarbonyl)piperazin-1-yl)-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-methyl-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (0.51 g, 0.842 mmol, 82 % yield) was prepared as described in the preparation of Intermediate 1M using tert-butyl 5-(4-(tert-butoxycarbonyl)piperazin-1-yl)-3-isopropyl-4-methyl-2-(4,4,5,5-tetramethyl-15-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (0.6 g, 1.026 mmol) and 6-bromo-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (0.281 g, 1.232 mmol) as the starting intermediates. LCMS retention time 2.23 min [L]. MS (E^-) m/z: 606.5 (M+H).
Example 213:
• 6-(3-isopropyl-4-methyl-5-(piperazin-1-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (1.4 mg, 3.45 µmol, 10.46 % yield) was prepared as described in the preparation of Example 4 using tert-butyl 5-(4-(tert-butoxycarbonyl) piperazin-1-yl)-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-methyl-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (20 mg, 0.033 mmol) as the starting intermediate. LCMS retention time 1.055 min [D4]. MS (E^-) m/z: 406.2 (M+H). ¹H NMR (400MHz, DMSO-d₆) δ 11.44 (s, 1H), 8.69 (d, J=1.5 Hz, 1H), 8.54 (s, 1H), 8.34 (s, 1H), 7.15 (d, J=1.5 Hz, 1H), 4.04 (s, 3H), 3.62 (d, J=7.0 Hz, 1H), 2.92-2.86 (m, 8H), 2.66 (s, 4H), 1.26 (d, J=7.0 Hz, 6H).
• The examples in Table 1 were prepared according to the general procedures described in the above examples. Examples 8-9 are not according to the present invention. TABLE 1

  Ex. No.	Structure	Mol. Wt.	LCMS M+	Ret Time (min)	HPLC Method
  8		408.55	409.3	0.76	QC-ACN-TFA-XB
  9		490.69	491.4	1.35	QC-ACN-AA-XB
  10		479.56	480.3	1.2	P
  11		461.57	462	1.591	P
  12		475.6	476.1	1.476	P
  13		406.51	407	0.897	Q
  14		514.62	515.3	1.53	P
  15		463.56	464.3	1.461	P
  16		460.58	461.1	1.766	P
  17		492.6	493.3	1.551	P
  18		450.56	451.3	1.285	P
  19		465.53	466.3	1.38	P
  20		479.56	480.3	1.442	P
  21		466.56	467.3	1.363	P
  22		491.62	492.3	1.457	P
  23		445.57	446.1	1.559	P
  24		489.62	490.1	1.599	P
  25		510.66	511	1.742	P
  26		459.6	460.1	1.637	P
  27		459.6	460.2	1.401	P
  28		388.52	389.1	1.323	P
  29		491.62	492.3	1.369	P
  30		444.58	445.1	1.745	P
  31		473.63	474.2	1.578	P
  32		489.62	490.2	1.533	P
  33		446.6	447.1	1.537	P
  34		493.59	494.3	1.381	P
  35		430.6	431.1	1.491	P
  36		473.63	474.2	1.493	P
  37		493.59	494.3	1.289	P
  38		464.55	465.3	1.571	P
  39		463.56	464.3	1.259	P
  40		476.59	477.3	1.371	P
  41		474.51	475.2	2.113	P
  42		479.56	480.3	1.383	P
  43		477.59	478.3	1.492	P
  44		489.6	490.3	1.394	P
  45		506.63	507.4	1.426	P
  46		462.57	463.3	1.31	P
  47		507.66	508.4	1.921	P
  48		476.64	477.4	1.875	P
  49		478.62	479.4	1.367	P
  50		502.64	503.3	1.421	P
  51		461.59	462	1.368	p
  52		477.63	478	1.434	p
  53		485.64	486.4	1.573	p
  54		501.68	502.4	1.448	p
  55		459.64	460.4	1.381	p
  56		485.64	486.3	1.796	p
  57		498.68	499	1.402	p
  58		486.71	487.4	1.625	p
  59		474.61	475.3	1.273	p
  60		460.63	461	1.38	p
  61		458.65	459.3	1.532	p
  62		488.64	489.4	1.057	p
  63		446.6	447.3	1.381	p
  64		523.66	524.4	1.396	p
  65		477.59	478.3	1.329	p
  66		477.59	478.3	1.43	p
  67		507.61	508.3	1.348	p
  68		463.61	464.3	1.346	p
  69		449.58	450.4	1.32	p
  70		447.56	448.3	1.276	p
  71		421.52	422.3	1.2	p
  72		522.63	523.3	1.382	p
  73		464.59	465.3	1.331	p
  74		494.62	495.3	1.331	P
  75		462.57	463.3	1.514	P
  76		478.62	479.4	1.605	P
  77		464.59	465.3	1.543	P
  78		493.59	494	1.828	P
  79		521.64	522	1.68	P
  80		462.57	463.3	1.511	P
  81		476.6	477.3	1.576	P
  82		490.63	491.3	1.362	P
  83		463.61	464	1.399	P
  84		476.64	477.4	1.844	P
  85		462.62	463	1.738	P
  86		475.64	476	1.298	P
  87		459.6	460	1.427	P
  88		489.67	490	1.361	P
  89		522.67	523.4	1.331	P
  90		458.65	459.3	1.319	P
  91		472.64	473.4	1.686	P
  92		488.68	489.4	1.606	P
  93		446.56	447.3	1.329	P
  94		474.61	475	1.597	P
  95		460.63	461.4	1.645	P
  96		476.63	477.4	1.346	P
  97		408.57	409.3	1.461	P
  98		476.59	477	1.145	P
  99		481.58	482.2	1.265	P
  100		507.61	508.3	1.263	P
  101		479.6	480.3	1.295	P
  102		465.58	466.4	1.264	P
  103		493.59	494.2	1.642	D
  104		493.59	494.3	1.529	P
  105		492.6	493.3	1.515	P
  106		492.6	493.4	1.912	P
  107		462.57	463.3	1.8	P
  108		462.62	463.3	1.607	P
  109		446.57	447.3	1.352	P
  110		490.63	491.3	1.599	P
  111		503.63	504.4	1.476	P
  112		473.67	474	1.777	P
  113		459.64	460	1.357	P
  114		517.61	518	1.967	P
  115		517.61	518.3	1.746	P
  116		460.63	461.4	1.503	P
  117		522.67	523.3	1.602	P
  118		472.59	473.3	1.249	P
  119		500.69	501.4	1.355	P
  120		500.69	501	1.615	P
  121		472.64	473.4	1.39	P
  122		488.68	489.4	1.371	P
  123		476.63	477	1.479	P
  124		459.64	460	1.546	P
  125		449.53	450.3	1.424	P
  126		463.59	464	1.46	P
  127		490.51	491.3	2.054	P
  128		464.59	465.3	1.432	P
  129		491.62	492.3	1.41	P
  130		477.59	478.3	1.582	P
  131		507.61	508	1.886	P
  132		488.61	489.3	1.707	P
  133		488.61	489.3	1.392	P
  134		504.65	505.4	1.381	P
  135		462.62	463.4	1.528	P
  136		462.62	463	1.488	P
  137		475.6	476.3	1.497	P
  138		461.61	462.3	1.482	P
  139		501.64	502.3	1.505	P
  140		459.6	460	1.596	P
  141		472.59	473.3	1.208	P
  142		498.68	499.4	1.691	P
  143		458.65	459.3	1.633	P
  144		460.63	461.4	1.564	P
  145		446.6	447.3	1.215	P
  146		477.59	478	1.508	P
  147		503.65	504.4	1.558	P
  148		469.64	470.3	1.856	P
  149		498.62	499.3	1.572	P
  150		437.56	438.3	1.605	P
  151		366.48	367.3	1.209	P
  152		423.54	424	1.532	P
  153		451.59	452.3	1.579	P
  154		490.61	491	1.243	P
  155		462.56	463	1.312	P
  156		495.6	496.4	1.255	P
  157		465.58	466.4	1.267	P
  158		478.58	479.3	1.48	P
  159		464.59	465.3	1.573	P
  160		506.63	507.3	1.312	P
  161		504.61	505.3	1.661	P
  162		492.64	493.3	1.601	P
  163		448.59	449.3	1.408	P
  164		478.62	479.4	1.604	P
  165		460.6	461.3	1.37	P
  166		463.61	464	1.396	P
  167		491.66	492	1.695	P
  168		476.64	477.3	1.497	P
  169		489.67	490.4	1.656	P
  170		487.65	488.4	1.563	P
  171		504.65	505	1.728	P
  172		504.65	505.4	2.077	P
  173		503.7	504	1.539	P
  174		476.6	477.3	1.568	P
  175		524.66	525.4	1.817	P
  176		502.66	503.4	1.504	P
  177		432.57	433	1.382	P
  178		446.56	447	1.277	P
  179		476.63	477.3	1.293	P
  180		488.64	489.4	1.248	P
  181		463.56	464.3	1.49	P
  182		448.55	449.3	1.631	P
  183		450.56	451.3	1.406	P
  184		392.48	393.2	1.111	P
  185		451.59	452.3	1.432	P
  186		511.65	512.3	1.451	P
  187		476.6	477.3	0.953	Q
  188		493.59	494.3	1.456	P
  189		501.56	502.3	1.938	P
  190		493.59		1.593	D
  191		437.52	438.3	1.162	P
  192		492.6	493.3	1.832	P
  193		506.63	507.3	1.384	P
  194		506.63	507.3	1.562	P
  195		494.62	495.4	1.565	P
  196		491.66	492.4	1.982	P
  197		492.6	493.3	1.661	P
  198		448.59	449.3	1.624	P
  199		448.59	449.3	1.45	P
  200		490.67	491.4	1.676	P
  201		503.65	504.4	1.346	P
  202		461.61	462	1.451	P
  203		500.69	501.4	1.726	P
  204		500.69	501.4	1.437	P
  205		501.68	502	1.333	P
  206		504.68	505.3	1.659	P
  207		504.68	505.4	1.413	P
  208		472.59	473.3	1.394	P
  209		472.59	473.3	1.32	P
  210		460.63	461.3	1.415	P
  211		476.63	477.3	1.518	P
  212		434.56	435.3	1.322	P
  213		405.51	406.2	1.055	P
  214		437.56	438.3	1.35	P
  215		450.6	451.3	1.798	P
  216		424.56	425	1.558	P
  217		492.6	493.3	1.333	P
  218		451.55	452.3	1.21	P
  219		449.58	450.3	1.313	P
  220		491.62	492.4	1.308	P
  221		508.6	509.3	1.532	P
  222		494.58	495.3	1.419	P
  223		478.57		1.756	P
  224		478.57	479.3	1.465	P
  225		506.63	507.4	1.692	P
  226		504.61	505.3	1.348	P
  227		478.62	479.3	1.394	P
  228		464.59	465	1.371	P
  229		492.64	493.3	1.833	P
  230		448.59	449.3	1.385	P
  231		476.6	477.3	1.886	P
  232		504.65	505.4	1.678	P
  233		460.6	461.3	1.58	P
  234		490.67	491.4	1.924	P
  235		445.62	446	1.535	P
  236		445.62	446.3	1.504	P
  237		473.63	474	1.494	P
  238		486.64	487.4	2.289	P
  239		486.64	487.3	1.888	P
  240		524.66	525.4	1.505	P
  241		502.66	503.4	1.233	P
  242		474.61	475.4	1.605	P
  243		474.61	475.4	1.337	P
  244		492.64	493.4	1.821	P
  245		500.65	501.3	1.546	P
  246		500.65	501.3	1.26	P
  247		486.71	487.4	1.625	P
  248		432.57	433.3	1.246	P
  249		432.57	433.3	1.367	P
  250		476.6	477.3	1.626	P
  251		422.55	423.2	1.768	P
  252		490.61	491	1.429	P
  253		463.56	464.2	1.241	P
  254		505.6	506.3	1.34	P
  255		463.56	464.3	1.428	P
  256		435.55	436.3	1.269	P
  257		485.56	486.3	2.006	P
  258		479.6	480.4	1.303	P
  259		492.6	493.2	1.584	P
  260		476.64	477.4	1.269	P
  261		462.62	463.3	2.006	P
  262		446.57	447.3	1.303	P
  263		462.62	463	1.727	P
  264		505.64	506	1.406	P
  265		487.65	488	1.545	P
  266		520.65	503.3	1.532	P
  267		476.6	477.3	1.966	P
  268		460.63	461.4	1.321	P
  269		502.66	503.4	1.584	P
  270		502.66	503.4	1.303	P
  271		492.64	493.4	1.3	P
  272		432.57	433	1.529	P
  273		446.56	447	1.335	P
  274		446.56	447.3	1.32	P
  275		474.61	475.4	1.378	P
  276		474.61	475	1.251	P
  277		458.65	459.4	1.255	P
  278		489.62	490.3	1.525	P
  279		443.6	444.3	1.466	P
  280		470.63	471.4	1.99	P
  281		521.68	522.3	1.15	Q
  282		473.63	474.3	1	Q
  283		475.64	476.4	1.191	Q
  284		486.62	487.3	1.107	Q
  285		550.73	551.3	1.828	P
  286		484.65	485.4	1.209	Q
  287		445.57	446.2	1.498	P
  288		462.56	462.1	2.369	P
  289		462.56	462.1	2.37	P
  290		497.62	498.2	1.228	P
  291		497	497	1.491	P
  292		461.57	462.2	1.453	P
  293		497	497.3	0.935	P
  294		532.06	532.1	1.827	P
  295		391.48	392.1	1.181	P
  296		462.6	463.2	1.376	P
  297		460.59	461.2	1.423	P
  298		475.6	476.2	1.393	P
  299		459.6	460.2	1.424	P
  300		476.59	477.3	1.241	P
  301		375.48	376	1.155	P
  302		446.56	447.2	1.406	P
  303		447.54	447.2	1.227	P
  304		511.03	511.2	1.626	P
  305		511.03	511.1	1.813	P
  306		446.56	447.1	1.577	P
  307		447.59	448.3	1.113	P
  308		460.58	461.3	1.417	P
  309		486.62	487	1.401	P
  310		474.65	475	1.624	P
  311		442.61	443.3	1.43	P
  312		390.49	391.3	0.916	P
  313		475.64	476.3	1.325	P
  314		475.6	476.3	1.405	P
  315		446.6	447.4	1.401	P
  316		446.6	447.4	1.332	P
  317		474.61	475	1.397	P
  318		444.63	445.3	1.333	P
  319		448.53	449.2	1.106	P
  320		461.57	462.3	1.197	P
  321		489.62	490	1.102	P
  322		489.62	490.3	1.212	P
  323		446.6	447.3	1.258	P
  324		444.58	445.3	1.19	P
  325		474.65	475	1.452	P
  326		444.63	445.3	1.489	P
  327		472.64	473	1.752	P
  328		489.62	490.3	1.596	P
  329		476.59	477.3	1.116	P
  330		460.58	461.4	1.309	P
  331		446.6	447	1.247	P
  332		444.58	445.3	1.318	P
  333		490.61	491.3	1.124	P
  334		458.61	459	1.456	P
  335		442.61	443.4	1.562	P
  336		466.58	467	2.17	P
  337		472.68	473.4	1.657	P
  338		489.62	490.3	1.443	P
  339		476.59	477.3	1.007	P
  340		432.57	433.3	1.194	P
  341		430.56	431.1	1.622	P
  342		474.61	475	1.23	P
  343		475.6	476.3	1.092	P
  344		490.61	491.3	1.208	P
  345		462.56	463.3	1.036	P
  346		458.61	459	1.616	P
  347		460.63	461.4	1.709	P
  348		460.63	461	1.332	P
  349		472.64	473	1.403	P
  350		466.58	467	1.794	P
  351		472.68	473.4	1.728	P

EXAMPLE 352 2-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-4-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl)piperazin-1-yl)-N,N-dimethylacetamide
• 
Intermediate 352A: tert-butyl 4-(3-isopropyl-4-methyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperazine-1-carboxylate
• 
• tert-butyl5-(4-(tert-butoxycarbonyl)piperazin-1-yl)-3-isopropyl-4-methyl-2-(4,4, 5, 5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (0.68 g, 1.163 mmol) was taken in a sealed tube and heated at 160 °C for 15 min to afford tert-butyl 4-(3-isopropyl-4-methyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-c] pyridin-5-yl)piperazine-1-carboxylate (0.56g, 1.152 mmol, 99% yield). LCMS retention time 1.64 min [L]. MS (E^-) m/z: 485.4 (M+H).
Intermediate 352B: tert-butyl 4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-4-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl)piperazine-1-carboxylate
• 
• tert-butyl4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-4-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl)piperazine-1-carboxylate (0.43 g, 0.854 mmol, 75 % yield) was prepared as described in the preparation of Intermediate 213I using tert-butyl 4-(3-isopropyl-4-methyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperazine-1-carboxylate (0.55 g, 1.135 mmol) and 6-bromo-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (0.308 g, 1.362 mmol) as the starting intermediates. LCMS retention time 1.99 min [L]. MS (E^-) m/z: 504.4 (M+H).
Intermediate 3 52C: 6-(3-isopropyl-4-methyl-5-(piperazin-1-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine
• 
• 6-(3-isopropyl-4-methyl-5-(piperazin-1-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (0.31 g, 0.768 mmol, 90 % yield) was prepared as described in the preparation of Example 4 using tert-butyl 4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-4-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl) piperazine-1-carboxylate (0.43 g, 0.854 mmol) as the starting intermediate. LCMS retention time 0.95 min [L]. MS (E^-) m/z: 404.4 (M+H).
Example 352:
• 2-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-4-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl)piperazin-1-yl)-N,N-dimethylacetamide (16.9 mg, 0.035 mmol, 55.8 % yield) was prepared as described in the preparation of Example 2 using 6-(3-isopropyl-4-methyl-5-(piperazin-1-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (25 mg, 0.062 mmol) and 2-chloro-N,N-dimethylacetamide (15.06 mg, 0.124 mmol) the starting intermediates. LCMS retention time 1.539 min [D4]. MS m/z: 489.3 [M+H]⁺; ¹H NMR (400MHz, DMSO-d₆) δ 11.96-11.83 (m, 1H), 8.95 (s, 1H), 8.52 (s, 1H), 8.49 (s, 1H), 4.40 (s, 2H), 3.42-3.26 (m, 9H), 2.99 (s, 3H), 2.95 (s, 3H), 2.70 (s, 3H), 2.61 (s, 3H), 2.16-2.05 (m, 3H), 1.24 (d, J=7.1 Hz, 3H), 1.02 (d, J=6.8 Hz, 3H).
EXAMPLE 353 6-(4-fluoro-3-isopropyl-5-(piperazin-1-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine
• 
Intermediate 353A: 5-chloro-4-fluoro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-c] pyridine
• 
• 5-chloro-4-fluoro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-c]pyridine (9.6 g, 31.9 mmol, 91 % yield) was prepared as described in the preparation of Intermediate 213A using 5-chloro-4-fluoro-1H-pyrrolo[2,3-c]pyridine (6 g, 35.2 mmol) as the starting material. LCMS retention time min 2.17[L]. MS (E^-) m/z: 301.2 (M+H).
Intermediate 353B: 3-bromo-5-chloro-4-fluoro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-c]pyridine
• 
• 3-bromo-5-chloro-4-fluoro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-c] pyridine (5.65 g, 14.88 mmol, 90 % yield) as brown solid was prepared as described in the preparation of Intermediate 213C using 5-chloro-4-fluoro-1-((2-(trimethylsilyl)ethoxy) methyl)-1H-pyrrolo[2,3-c]pyridine (5 g, 16.62 mmol) as the starting intermediate. LCMS retention time 381.1 min [L]. MS (E^-) m/z: (M+2H).
Intermediate 353C: 5-chloro-4-fluoro-3-(prop-1-en-2-yl)-1-((2-(trimethylsilyl)ethoxy) methyl)-1H-pyrrolo[2,3-c]pyridine
• 
• 5-chloro-4-fluoro-3-(prop-1-en-2-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-c]pyridine (6.0 g, 17.60 mmol, 84 % yield) was prepared as described in the preparation of Intermediate 213D using 3-bromo-5-chloro-4-fluoro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-c]pyridine (8.0 g, 21.07 mmol) and 4,4,5,5-tetramethyl-2-(prop-1-en-2-yl)-1,3,2-dioxaborolane (3.54 g, 21.07 mmol) as the starting intermediates. LCMS retention time 1.48 min [L]. MS (E^-) m/z: 341.1 (M+H).
Intermediate 353D: 5-chloro-4-fluoro-3-isopropyl-1-((2-trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-c]pyridine
• 
• 5-chloro-4-fluoro-3-isopropyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-c]pyridine (5.82 g, 13.92 mmol, 79 % yield) was prepared as described in the preparation of Intermediate 213E using 5-chloro-4-fluoro-3-(prop-1-en-2-yl)-1-((2-(trimethylsilyl)ethoxy) methyl)-1H-pyrrolo[2,3-c]pyridine (6.0 g, 17.60 mmol) as the starting intermediate. LCMS retention time 1.61 min [L]. MS (E^-) m/z: 343.5 (M+H).
Intermediate 353E: tert-butyl 4-(4-fluoro-3-isopropyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperazine-1-carboxylate
• 
• tert-butyl 4-(4-fluoro-3-isopropyl-1-((2-(trimthylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperazine-1-carboxylate (3.6 g, 7.31 mmol, 84 % yield) was prepared as described in the preparation of Intermediate 213B using 5-chloro-4-fluoro-3-isopropyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-c]pyridine (3.000 g, 8.75 mmol) and tert-butyl piperazine-1-carboxylate (1.955 g, 10.50 mmol) as the starting intermediates. LCMS retention time 1.81 min [L]. MS (E^-) m/z: 493.9 (M+H).
Intermediate 353F: tert-butyl 4-(4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-5-yl) piperazine-1 -carboxylate
• 
• tert-butyl 4-(4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-5-yl)piperazine-1-carboxylate (2.1 g, 5.79 mmol, 95 % yield) was prepared as described in the preparation of Intermediate 213F using tert-butyl 4-(4-fluoro-3-isopropyl-1-((2-(trimethylsilyl) ethoxy)methyl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperazine-1-carboxylate (3.0 g, 6.09 mmol) as the starting intermediate. LCMS retention time 1.81 min [L]. MS (E^-) m/z: 363.2 (M+H).
Intermediate 353G: tert-butyl 5-(4-(tert-butoxycarbonyl)piperazin-1-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridine-1-carboxylate
• 
• tert-butyl 5-(4-(tert-butoxycarbonyl)piperazin-1-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (2.3 g, 4.97 mmol, 90 % yield) was prepared according to the general procedure described in Intermediate 1I using tert-butyl 4-(4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-5-yl)piperazine-1-carboxylate (2 g, 5.52 mmol) as the starting intermediate. LCMS retention time 1.87 min [L]. MS m/z: 463.4 [M+H]⁺.
Intermediate 353H: tert-butyl 5-(4-(tert-butoxycarbonyl)piperazin-1-yl)-4-fluoro-3-isopropyl-2-(4,4, 5, 5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-c]pyridine-1-carboxylate
• 
• tert-butyl 5-(4-(tert-butoxycarbonyl)piperazin-1-yl)-4-fluoro-3-isopropyl-2-(4,4, 5, 5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (1.45 g, 2.464 mmol, 92 % yield) was prepared according to the general procedure described in Intermediate 1L using tert-butyl 5-(4-(tert-butoxycarbonyl)piperazin-1-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (1.24 g, 2.68 mmol) as the starting intermediate. LCMS retention time 2.127 min [D]. MS m/z: 589.2 [M+H]⁺.
Intermediate 353I: tert-butyl 5-(4-(tert-butoxycarbonyl)piperazin-1-yl)-4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridine-1-carboxylate
• 
• tert-butyl 5-(4-(tert-butoxycarbonyl)piperazin-1-yl)-4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (0.85 g, 1.394 mmol, 70.7 % yield) was prepared according to the general procedure described in Intermediate 1M using tert-butyl 5-(4-(tert-butoxycarbonyl)piperazin-1-yl)-4-fluoro-3-isopropyl-2-(4,4,5,5-tetramethyl-15-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (1.16 g, 1.971 mmol) as the starting intermediate. LCMS retention time 1.37 min [L]. MS m/z: 610.5 [M+H]⁺.
Example 353:
• 6-(4-fluoro-3-isopropyl-5-(piperazin-1-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (0.27 g, 0.653 mmol, 93% yield) was prepared according to the general procedure described in the preparation of Example 4 using tert-butyl 5-(4-(tert-butoxycarbonyl)piperazin-1-yl)-4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (0.43 g, 0.705 mmol) as the starting intermediate. LCMS retention time 1.270 min [D4]. MS m/z: 410.3 [M+H]⁺; ¹H NMR (400MHz, DMSO-d₆) δ 11.79 (br. s., 1H), 8.70 (d, J=1.2 Hz, 1H), 8.55 (s, 1H), 8.32 (d, J=1.5 Hz, 1H), 7.18 (s, 1H), 4.07 (s, 3H), 3.28 (dd, J=7.3, 3.9 Hz, 1H), 3.18-3.11 (m, 5H), 2.98-2.86 (m, 4H), 1.34 (d, J=6.8 Hz, 6H).
• The following Example was prepared according to the general procedure used to prepare Example 353:

  Ex. No.	structure	LCMS (M+H)	RT	HPLC method
  354		424.3	0.91	L

EXAMPLE 3 5 5 6-(4-fluoro-3-isopropyl-5-(2,6-diazaspiro[3.3]heptan-2-yl)-1H-pyrrolo[2,3 -c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine
• 
Intermediate 355A: tert-butyl 6-(4-fluoro-3-isopropyl-1-((2-(trimethylsilyl)ethoxy) methyl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-2,6-diazaspiro[3.3]heptane-2-carboxylate
• 
• tert-butyl 6-(4-fluoro-3-isopropyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-2,6-diazaspiro[3.3]heptane-2-carboxylate (6.66 g, 13.20 mmol, 94 % yield) was prepared as described in the preparation of Intermediate 213B using 5-chloro-4-fluoro-3-isopropyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-c]pyridine (4.8 g, 14.00 mmol) and tert-butyl 2,6-diazaspiro[3.3]heptane-2-carboxylate (3.33 g, 16.80 mmol) as starting materials. LCMS retention time 1.69 min [L]. MS (E^-) m/z: 505.7 (M+H).
• The following Intermediates were prepared according to the general procedure used to prepare Intermediate 355A:

  Int.	Structure	LCMS (M+H)	RT	HPLC method
  393A		493.9	1.81	L
  393A		507.9	1.92	L

Intermediate 355B: tert-butyl 6-(4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-5-yl)-2,6-diazaspiro[3.3]heptane-2-carboxylate
• 
• tert-butyl 6-(4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-5-yl)-2,6-diazaspiro[3.3]heptane-2-carboxylate (5.0 g, 12.15 mmol, 92 % yield) was prepared as described in the preparation of Intermediate 213F using tert-butyl 6-(4-fluoro-3-isopropyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-2,6-diazaspiro[3.3]heptane-2-carboxylate (6.66 g, 13.20 mmol) as a starting material. LCMS retention time 0.93 min [L]. MS (E^-) m/z: 375.3 (M+H).
Intermediate 355C: tert-butyl 5-(6-(tert-butoxycarbonyl)-2,6-diazaspiro[3.3]heptan-2-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridine-1-carboxylate
• 
• tert-butyl 5-(6-(tert-butoxycarbonyl)-2,6-diazaspiro[3.3]heptan-2-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (4 g, 8.43 mmol, 63.1 % yield) was prepared as described in the preparation of Intermediate 1I using tert-butyl 6-(4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-5-yl)-2,6-diazaspiro[3.3]heptane-2-carboxylate (5 g, 13.35 mmol) as a starting material. LCMS retention time 1.71 min [L]. MS (E^-) m/z: 475.3 (M+H).
Intermediate 355D: tert-butyl 5-(6-(tert-butoxycarbonyl)-2,6-diazaspiro[3.3]heptan-2-yl)-4-fluoro-3-isopropyl-2-(4,4,5,5-tetramethyl-15-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-c] pyridine-1-carboxylate
• 
• tert-butyl 5-(6-(tert-butoxycarbonyl)-2,6-diazaspiro[3.3]heptan-2-yl)-4-fluoro-3-isopropyl-2-(4,4, 5, 5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (4.5 g, 7.49 mmol, 89 % yield) was prepared as described in the preparation of Intermediate 1L using tert-butyl 5-(6-(tert-butoxycarbonyl)-2,6-diazaspiro[3.3]heptan-2-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (4.0 g, 8.43 mmol) as the starting material. LCMS retention time 2.834 min [D]. MS (E^-) m/z: 601.4 (M+H).
Intermediate 355E: tert-butyl 5-(6-(tert-butoxycarbonyl)-2,6-diazaspiro[3.3]heptan-2-yl)-4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c] pyridine-1-carboxylate
• 
• tert-butyl 5-(6-(tert-butoxycarbonyl)-2,6-diazaspiro[3.3]heptan-2-yl)-4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (1.4 g, 2.252 mmol, 67.6 % yield) was prepared as described in the preparation of Intermediate 1M using tert-butyl 5-(6-(tert-butoxycarbonyl)-2,6-diazaspiro[3.3]heptan-2-yl)-4-fluoro-3-isopropyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (2.0 g, 3.33 mmol) and 6-bromo-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (0.835 g, 3.66 mmol) as starting materials. LCMS retention time 1.12 min [L]. MS (E^-) m/z: 622.4 (M+H).
Example 355:
• 6-(4-fluoro-3-isopropyl-5-(2,6-diazaspiro[3.3]heptan-2-yl)-1H-pyrrolo[2,3-c] pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (0.55 g, 1.305 mmol, 62.4 % yield) was prepared according to the general procedure described in the preparation of Example 4 using tert-butyl 5-(6-(tert-butoxycarbonyl)-2,6-diazaspiro[3.3]heptan-2-yl)-4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c] pyridine-1-carboxylate (1.3 g, 2.091 mmol) in DCM (15 mL) as starting material. LCMS retention time 0.83 min [L]. MS (E^-) m/z: 422.3 (M+H).
EXAMPLE 356 2-(6-(4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-2,6-diazaspiro[3.3]heptan-2-yl)-N-methylacetamide
• 
• 2-(6-(4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-2,6-diazaspiro[3.3]heptan-2-yl)-N-methylacetamide (3.1 mg, 6.04 µmol, 8.49 % yield) was prepared as described in the preparation of Example 2 using 6-(4-fluoro-3-isopropyl-5-(2,6-diazaspiro[3.3]heptan-2-yl)-1H-pyrrolo[2,3-c] pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (30 mg, 0.071 mmol) and 2-chloro-N-methylacetamide (11.48 mg, 0.107 mmol) as the starting intermediates. LCMS retention time 1.322 min [P]. MS m/z: 493.3 [M+H]⁺; ¹H NMR (400 MHz, DMSO-d₆) δ = 11.62 (d, J = 1.2 Hz, 1H), 8.69 (s, 1H), 8.55 (s, 1H), 8.22 (d, J = 1.7 Hz, 1H), 7.70-7.55 (m, 1H), 7.17 (s, 1H), 4.11-4.03 (m, 8H), 3.43 (s, 4H), 3.28-3.20 (m, 1H), 3.01 (s, 2H), 2.60 (d, J = 4.9 Hz, 2H), 1.33 (d, J = 7.3 Hz, 6H).
• The following Examples were prepared according to the general procedure used to prepare Example 356:

  Ex. No.	Structure	LCMS (M+H)	RT	HPLC method
  357		528.2	1.397	D4
  358		467.3	1.486	D4
  359		481.3	1.558	D4
  360		495.3	1.62	D4
  361		468.3	1.699	D4
  362		516.3	1.617	D4
  363		537.3	1.616	D4
  364		482.3	1.781	D4
  365		449.2	1.558	D4
  366		492.2	2.023	D4

EXAMPLE 367 1-(6-(4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-2,6-diazaspiro[3.3]heptan-2-yl)-2-morpholinoethan-1-one
• 
• 1-(6-(4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-2,6-diazaspiro[3.3]heptan-2-yl)-2-morpholinoethan-1-one (2.3 mg, 4.19 µmol, 5.89 % yield) was prepared as described in the preparation of Example 5 using 6-(4-fluoro-3-isopropyl-5-(2,6-diazaspiro[3.3]heptan-2-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (30 mg, 0.071 mmol) and 2-morpholinoacetic acid (15.50 mg, 0.107 mmol) as the starting intermediates. LCMS retention time 1.407 min [P]. MS m/z: 549.3 [M+H]⁺; ¹H NMR (400 MHz, DMSO-d₆) δ = 11.64 (s, 1H), 8.69 (s, 1H), 8.55 (s, 1H), 8.23 (d, J = 1.7 Hz, 1H), 7.18 (s, 1H), 4.41 (s, 2H), 4.13 (s, 4H), 4.08 (s, 5H), 3.59 (br d, J = 3.4 Hz, 6H), 2.99 (br d, J = 1.7 Hz, 2H), 2.43 (br d, J = 2.2 Hz, 3H), 1.33 (d, J = 7.1 Hz, 6H).
• The following Example was prepared according to the general procedure used to prepare Example 367:

  Ex. No.	Structure	LCMS (M+H)	RT	HPLC method
  368		495.3	1.453	D4

EXAMPLE 369 6-(4-fluoro-3-isopropyl-5-(6-(oxetan-3-yl)-2,6-diazaspiro[3.3]heptan-2-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine
• 
• 6-(4-fluoro-3-isopropyl-5-(6-(oxetan-3-yl)-2,6-diazaspiro[3.3]heptan-2-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (8.2 mg, 0.017 mmol, 23.88 % yield) was prepared as described in the preparation of Example 42 using 6-(4-fluoro-3-isopropyl-5-(2,6-diazaspiro[3.3]heptan-2-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (30 mg, 0.071 mmol) and oxetan-3-one (10.26 mg, 0.142 mmol) as the starting intermediates. LCMS retention time 1.410 min [P]. MS m/z: 478.2 [M+H]⁺; ¹H NMR (400 MHz, DMSO-d₆) δ = 11.62 (s, 1H), 8.69 (d, J = 0.7 Hz, 1H), 8.55 (s, 1H), 8.22 (d, J = 2.0 Hz, 1H), 7.17 (s, 1H), 4.55 (t, J = 6.5 Hz, 2H), 4.35 (t, J = 5.7 Hz, 2H), 4.07 (s, 7H), 3.73-3.64 (m, 1H), 3.39 (s, 4H), 3.25 (dt, J = 4.6, 6.8 Hz, 1H), 1.33 (d, J = 7.1 Hz, 6H).
• The following Examples were prepared according to the general procedure used to prepare Example 369:

  Ex. No.	Structure	LCMS (M+H)	RT	HPLC method
  370		506.2	1.429	D4
  371		520.3	1.402	D4
  372		478.3	1.415	D4
  373		464.3	1.282	D4
  374		476.3	1.332	D4
  375		490.3	1.494	D4
  376		506.3	1.459	D4
  377		547.4	1.318	D4
  378		436.2	1.166	D4
  379		450.2	1.240	D4
  380		464.2	1.376	D4
  381		476.2	1.467	D4
  382		466.3	11.642	D4
  383		508.3	11.872	D4
  384		452.3	11.619	D4
  385		494.3	11.847	D4
  386		494.3	11.661	D4
  387		494.3	11.663	D4
  388		535.3	11.302	D4
  389		438.3	11.401	D4
  390		464.2	11.607	D4
  391		464.2	11.722	D4

EXAMPLE 392 6-(4-fluoro-3-isopropyl-5-(2,6-diazaspiro[3.3]heptan-2-yl)-1H-pyrrolo[2,3 -c]pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine
• 
Intermediate 392A: tert-butyl 6-(4-fluoro-3-isopropyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-2,6-diazaspiro[3.3]heptane-2-carboxylate
• 
• tert-Butyl 5-(6-(tert-butoxycarbonyl)-2,6-diazaspiro[3.3]heptan-2-yl)-4-fluoro-3-isopropyl-2-(4,4, 5, 5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (2.3 g, 3.83 mmol) was placed in a sealed tube and heated at 160 °C for 15 min. LCMS retention time 1.33 min [L]. MS (E^-) m/z: 501.4 (M+H).
Intermediate 392B: tert-butyl 6-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-5-yl)-2,6-diazaspiro[3.3]heptane-2-carboxylate
• 
• To a solution of tert-butyl 6-(4-fluoro-3-isopropyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-2,6-diazaspiro[3.3]heptane-2-carboxylate (1.9 g, 3.80 mmol) and 6-bromo-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (0.944 g, 4.18 mmol) in mixture of THF (30 mL) and water (3 mL) was added tripotassium phosphate (2.015 g, 9.49 mmol). The reaction mixture was purged with nitrogen for 5 mins, then chloro(2-dicyclohexylphosphino-2',4',6'-triisopropyl-1,1'-biphenyl)[2-(2'-amino-1,1'-biphenyl)]palladium(II) (0.299 g, 0.380 mmol) was added. The reaction mixture was purged again for 2 mins and then heated in a sealed tube at 75 °C for 1 h. The reaction mixture was filtered through Celite and diluted with EtOAc (50 mL) and washed with water (10 mL), and brine solutions (10 mL). The organic layer was dried over Na₂SO₄, filter and concentrated to give crude compound which was purified over silica gel eluting 5% MeOH in DCM. LCMS retention time 0.93 min [L]. MS (E^-) m/z: 520.3 (M+H).
• The following Intermediates were prepared according to the general procedure used to prepare Intermediate 392B:

  Int. No.	structure	LCMS (M+H)	RT	HPLC method
  393B		508.2	3.411	D
  394B		522.4	2.05	L

Example 392:
• 6-(4-fluoro-3-isopropyl-5-(2,6-diazaspiro[3.3]heptan-2-yl)-1H-pyrrolo[2,3-c] pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (0.79 g, 1.751 mmol, 79 % yield) was prepared as described in the preparation of Example 4 using tert-butyl 6-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-5-yl)-2,6-diazaspiro[3.3]heptane-2-carboxylate (1.15 g, 2.213 mmol) as the starting intermediate. LCMS retention time 1.163 min [D4]. MS (E^-) m/z: 420.1 (M+H). ¹H NMR (400 MHz, DMSO-d₆) δ ppm 11.38-11.56 (m, 1 H) 8.88 (s, 1 H) 8.50 (s, 1 H) 8.12-8.22 (m, 1 H) 4.01-4.15 (m, 4 H) 3.76 (s, 4 H) 2.81 (td, J=7.09, 3.67 Hz, 1 H) 2.59 (s, 3 H) 2.11-2.17 (m, 3 H) 1.77 (s, 1 H) 1.23 (br t, J=6.72 Hz, 6 H).
• The following Examples were prepared according to the general procedure used to prepare Example 392:

  Ex. No.	Structure	LCMS (M+H)	RT	HPLC method
  393		408.3	1.356	D4
  394		507.9	1.92	L

EXAMPLE 395 2-(6-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-5-yl)-2,6-diazaspiro[3.3]heptan-2-yl)-N-methylacetamide
• 
• 2-(6-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-5-yl)-2,6-diazaspiro[3.3]heptan-2-yl)-N-methylacetamide (3.9 mg, 7.95 µmol, 11 % yield) was prepared as described in the preparation of Example 2 using 6-(4-fluoro-3-isopropyl-5-(2,6-diazaspiro[3.3]heptan-2-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (30 mg, 0.072 mmol) and 2-chloro-N-methylacetamide (11.54 mg, 0.107 mmol) as the starting intermediates. LCMS retention time 1.057min [D4]. MS m/z: 491.3 [M+H]⁺; ¹H NMR (400 MHz, DMSO-d ₆) δ ppm 11.44 (d, J=0.98 Hz, 1 H) 8.88 (s, 1 H) 8.50 (s, 1 H) 8.18 (d, J=1.96 Hz, 1 H) 7.67-7.77 (m, 1 H) 4.02-4.13 (m, 4H) 3.50-3.61 (m, 3 H) 3.11-3.21 (m, 2 H) 2.81 (dtd, J=13.72, 6.89, 6.89, 3.79 Hz, 1 H) 2.58-2.63 (m, 6 H) 2.55 (s, 1 H) 2.14 (s, 3 H) 1.23 (t, J=6.60 Hz, 6H).
• The following Examples were prepared according to the general procedure used to prepare Example 395:

  Ex. No.	Structure	LCMS (M+H)	RT	HPLC method
  396		526.2	1.486	D4
  397		459.2	1.609	D4
  398		514.3	1.709	D4

EXAMPLE 399 1-(6-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-5-yl)-2,6-diazaspiro[3.3]heptan-2-yl)-2-morpholinoethan-1-one
• 
• 1-(6-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-5-yl)-2,6-diazaspiro[3.3]heptan-2-yl)-2-morpholinoethan-1-one (9.5 mg, 0.017 mmol, 23.6 % yield) was prepared as described in the preparation of Example 5 using 6-(4-fluoro-3-isopropyl-5-(2,6-diazaspiro[3.3]heptan-2-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (30 mg, 0.072 mmol) and 2-morpholinoacetic acid (15.57 mg, 0.107 mmol) as the starting intermediates. LCMS retention time 1.470 min [P]. MS m/z: 547.3 [M+H]⁺; ¹H NMR (400 MHz, DMSO-d ₆) δ ppm 11.46 (d, J=1.71 Hz, 1 H) 8.89 (s, 1 H) 8.50 (s, 1 H) 8.19 (d, J=1.96 Hz, 1 H) 4.40 (s, 2 H) 4.05-4.18 (m, 6 H) 3.56-3.63 (m, 4 H) 2.94-3.03 (m, 2 H) 2.76-2.86 (m, 1 H) 2.60 (s, 3 H) 2.39-2.47 (m, 4 H) 2.14 (s, 3 H) 1.20-1.27 (m, 6 H).
EXAMPLE 400 6-(4-fluoro-3-isopropyl-5-(6-(oxetan-3-yl)-2,6-diazaspiro[3.3]heptan-2-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine
• 
• 6-(4-fluoro-3-isopropyl-5-(6-(oxetan-3-yl)-2,6-diazaspiro[3.3]heptan-2-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (10.4 mg, 0.021 mmol, 28.7 % yield) was prepared as described in the preparation of Example 42 using 6-(4-fluoro-3-isopropyl-5-(2,6-diazaspiro[3.3]heptan-2-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (30 mg, 0.072 mmol) and oxetan-3-one (10.31 mg, 0.143 mmol) as the starting intermediates. LCMS retention time 1.498 min [D4]. MS m/z: 476.2 [M+H] ⁺; ¹H NMR (400 MHz, DMSO-d ₆) δ ppm 11.41-11.50 (m, 1 H) 8.89 (s, 1 H) 8.50 (s, 1 H) 8.17-8.23 (m, 1 H) 4.73-4.79 (m, 1 H) 4.53-4.64 (m, 2 H) 4.33-4.43 (m, 2 H) 4.03-4.11 (m, 3 H) 3.91-3.98 (m, 1 H) 3.65-3.76 (m, 1 H) 3.41 (br s, 3 H) 2.76-2.87 (m, 1 H) 2.59 (s, 3 H) 2.14 (s, 3 H) 1.23 (br t, J=6.60 Hz, 6 H).
• The following Examples were prepared according to the general procedure used to prepare Example 400:

  Ex. No.	Structure	LCMS (M+H)	RT	HPLC method
  401		504.3	1.511	D4
  402		476.3	1.586	D4
  403		462.3	1.128	D4
  404		488.3	1.623	D4
  405		504.3	1.608	D4
  406		545.3	1.408	D4
  407		434.2	1.262	D4
  408		448.2	1.322	D4
  409		464.3	1.738	D4
  410		492.3	1.949	D4
  411		506.3	1.968	D4
  412		450.3	1.702	D4

• The following Examples were prepared according to the general procedure used to prepare Example 352

  Ex. No.	Structure	LCMS (M+H)	RT	HPLC method
  413		475.3	1.542	D4
  414		461.3	1.480	D4
  415		510.2	2.176	D

EXAMPLE 416 1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-4-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl)piperazin-1-yl)-2-(dimethylamino)ethan-1-one
• 
• 1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-4-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl)piperazin-1-yl)-2-(dimethylamino)ethan-1-one (10 mg, 0.020 mmol, 16.35 % yield) was prepared as described in the preparation of Example 5 using 6-(3-isopropyl-4-methyl-5-(piperazin-1-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (50 mg, 0.124 mmol) and dimethylglycine (25.6 mg, 0.248 mmol) as the starting intermediates. LCMS retention time 1.939 min [D]. MS m/z: 489.2 [M+H] ⁺; ¹H NMR (400 MHz, DMSO-d₆) δ 11.30 (s, 1H), 8.85 (s, 1H), 8.46 (s, 1H), 8.29 (s, 1H), 3.99-4.16 (m, 1H), 3.56-3.83 (m, 4H), 3.05-3.22 (m, 3H), 2.80-3.03 (m, 6H), 2.63-2.71 (m, 5H), 2.30 (t, J=2.01 Hz, 1H), 2.20 (s, 3H), 2.08 (s, 3H), 1.19 (d, J=7.03 Hz, 3H), 0.98 (d, J=7.03 Hz, 3H).
EXAMPLE 417 6-(3-isopropyl-4-methyl-5-(4-(oxetan-3-yl)piperazin-1-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine
• 
• 6-(3-isopropyl-4-methyl-5-(4-(oxetan-3-yl)piperazin-1-yl)-1H-pyrrolo[2,3-c] pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (16.3 mg, 0.033 mmol, 66.8 % yield) was prepared as described in the preparation of Intermediate 2C with 6-(3-isopropyl-4-methyl-5-(piperazin-1-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (20 mg, 0.050 mmol) and oxetan-3-one (14.29 mg, 0.198 mmol) the starting intermediate. LCMS retention time 1.652 min [D4]. MS m/z: 460.3 [M+H]⁺; ¹H NMR (400MHz, DMSO-d₆) δ = 12.02-11.82 (m, 1H), 8.95 (s, 1H), 8.52 (s, 1H), 8.49 (s, 1H), 4.86-4.76 (m, 4H), 4.54-4.42 (m, 1H), 3.87 (br d, J=4.9 Hz, 1H), 3.37-3.26 (m, 8H), 2.71 (s, 3H), 2.61 (s, 3H), 2.14-2.07 (m, 3H), 1.24 (d, J=7.1 Hz, 3H), 1.02 (d, J=7.1 Hz, 3H).
• The following Examples were prepared according to the general procedure used to prepare Example 417:

  Ex. No.	Structure	LCMS (M+H)	RT	HPLC method
  418		488.3	1.630	D4
  419		502.3	1.790	D4

EXAMPLE 420 1-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c] pyridin-5-yl)piperidin-4-amine
• 
Intermediate 420A: tert-butyl (1-(4-methyl-5-nitropyridin-2-yl)piperidin-4-yl)carbamate
• 
• tert-butyl (1-(4-methyl-5-nitropyridin-2-yl)piperidin-4-yl)carbamate (1 g, 2.91 mmol, 63.2 % yield) was prepared as described in the preparation of Intermediate 6A using 2-bromo-4-methyl-5-nitropyridine (1 g, 4.61 mmol) and tert-butyl piperidin-4-ylcarbamate (0.923 g, 4.61 mmol) as starting material. LCMS retention time 1.41 min [B]. MS (E^-) m/z: 335.5 (M-H).
Intermediate 420B: tert-butyl(E)-(1-(4-(2-(dimethylamino)vinyl)-5-nitropyridin-2-yl) piperidin-4-yl)carbamate
• 
• (E)-tert-butyl (1-(4-(2-(dimethylamino)vinyl)-5-nitropyridin-2-yl)piperidin-4-yl) carbamate (13 g, 31.9 mmol, 46 % yield) was prepared as described in the preparation of Intermediate 6B using tert-butyl (1-(4-methyl-5-nitropyridin-2-yl)piperidin-4-yl) carbamate (23 g, 68.4 mmol) and 1,1-dimethoxy-N,N-dimethylmethanamine (45.8 mL, 342 mmol) as the starting intermediates. LCMS retention time 1.38 min [B], MS (E⁺) m/z: 392.6 (M+H).
Intermediate 420C: tert-butyl (1-(1H-pyrrolo[2,3-c]pyridin-5-yl)piperidin-4-yl) carbamate
• 
• tert-butyl (1-(1H-pyrrolo[2,3-c]pyridin-5-yl)piperidin-4-yl)carbamate (13 g, 27.5 mmol, 71.8 % yield) was prepared as described in the preparation of intermediate 6C using tert-butyl (E)-tert-butyl 4-(4-(2-(dimethylamino)vinyl)-5-nitropyridin-2-yl) piperazine-1-carboxylate (15 g, 39.7 mmol) as the starting intermediate. LCMS retention time 1.04 min [B], MS m/z: 317.5 (M+H).
Intermediate 420D: tert-butyl (1-(3-bromo-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidin-4-yl) carbamate
• 
• tert-butyl (1-(3-bromo-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidin-4-yl)carbamate (3 g, 7.59 mmol, 80% yield) was prepared as described in the preparation of Intermediate 6D using tert-butyl (1-(1H-pyrrolo[2,3-c]pyridin-5-yl)piperidin-4-yl)carbamate (3 g, 9.48 mmol) as the starting intermediate. LCMS retention time 1.28 min [B], MS (E^-) m/z: 397.4 (M+2H).
Intermediate 420E: tert-butyl3-bromo-5-(4-((tert-butoxycarbonyl)amino)piperidin-1-yl)-1H-pyrrolo[2,3 -c]pyridine-1 -carboxylate
• 
• tert-butyl 3-bromo-5-(4-((tert-butoxycarbonyl)amino)piperidin-1-yl)-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (2g, 4.04 mmol, 80% yield) was prepared as described in the preparation of Intermediate 6E using tert-butyl (1-(3-bromo-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidin-4-yl) carbamate (2 g, 5.06 mmol) as the starting intermediate. LCMS retention time 1.64 min [B], MS (E^-) m/z: 495.3 (M+H).
Intermediate 420F: tert-butyl5-(4-((tert-butoxycarbonyl)amino)piperidin-1-yl)-3-(prop-1-en-2-yl)-1H-pyrrolo[2,3-c]pyridine-1-carboxylate
• 
• tert-butyl 5-(4-((tert-butoxycarbonyl)amino)piperidin-1-yl)-3-(prop-1-en-2-yl)-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (1.6 g, 3.50 mmol, 83 % yield) was prepared as described in the preparation of Intermediate 6F using tert-butyl 3-bromo-5-(4-((tertbutoxycarbonyl)amino)piperidin-1-yl)-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (2.1 g, 4.24 mmol) as the starting intermediate. LCMS retention time 1.30 min [B], MS (E^-) m/z: 457.3 (M+H).
Intermediate 420G: tert-butyl 5-(4-((tert-butoxycarbonyl)amino)piperidin-1-yl)-3-isopropyl-1H-pyrrolo[2,3-c]pyridine-1-carboxylate
• 
• tert-butyl5-(4-((tert-butoxycarbonyl)amino)piperidin-1-yl)-3-isopropyl-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (1.6 g, 3.49 mmol, 88 % yield) was prepared as described in the preparation of Intermediate 6G using tert-butyl 5-(4-((tertbutoxycarbonyl)amino)piperidin-1-yl)-3-(prop-1-en-2-yl)-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (1.8 g, 3.94 mmol) as the starting intermediate. LCMS retention time 1.78 min [B], MS (E⁺) m/z: 459.6 (M+H).
Intermediate 420H: tert-butyl 5-(4-((tert-butoxycarbonyl)amino)piperidin-1-yl)-3-isopropyl-2-(4,4, 5, 5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-c]pyridine-1-carboxylate
• 
• tert-butyl 5-(4-((tert-butoxycarbonyl) amino)piperidin-1-yl)-3-isopropyl-2-(4,4, 5, 5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (280 mg, 0.053 mmol, 4.03 % yield) was prepared as described in the preparation of Intermediate 6I using tert-butyl 5-(4-((tert-butoxycarbonyl)amino)piperidin-1-yl)-3-isopropyl-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (600 mg, 1.308 mmol as the starting intermediate. LCMS retention time 2.10 min [B], MS (E^-) m/z: 586.8 (M+H).
Intermediate 420I: tert-butyl 5-(4-((tert-butoxycarbonyl)amino)piperidin-1-yl)-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridine-1-carboxylate
• 
• tert-butyl-5-(4-((tert-butoxycarbonyl)amino)piperidin-1-yl)-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a] pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (200 mg, 0.023 mmol) was prepared as described in the preparation of Intermediate 6J using tert-butyl 5-(4-((tert-butoxycarbonyl)amino)piperidin-1-yl)-3-isopropyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (523 mg, 0.895 mmol) and 6-bromo-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (245 mg, 1.074 mmol) as the starting intermediates. LCMS retention time 1.57 min [B], MS (E^-) m/z: 606.6 (M+H).
Example 420:
• 1-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidin-4-amine (145 mg, 0.318 mmol) was prepared according to the general procedure described in Example 4 using tert-butyl 5-(4-((tert-butoxycarbonyl) amino)piperidin-1-yl)-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (200 mg, 0.330 mmol) as starting material intermediate. LCMS retention time 0.68 min [B], MS (E⁺) m/z: 406.5 (M+H);
• The following examples were prepared according to the general procedures described in the above examples.

  Ex. No.	Structure	Obs. MS Ion	RT	QC Method
  421		535.3	1.59	E
  422		493.3	1.41	E
  423		535.3	1.56	E
  424		466.3	1.66	E
  425		486.2	1.67	E
  426		480.3	1.11	E
  427		450.2	1.55	E
  428		493.3	1.57	E
  429		465.2	1.43	E
  430		462.3	1.75	E
  431		492.1	1.64	E
  432		478.3	2.51	E
  433		436.3	1.54	E
  434		502.0	1.95	E
  435		505.0	1.34	E
  436		438.2	1.39	E
  437		466.2	1.64	E
  438		551.2	1.49	E
  439		509.3	1.31	E
  440		480.3	1.56	E
  441		478.3	1.82	E
  442		478.2	1.63	E
  443		466.3	1.52	E
  444		482.3	1.57	E
  445		495.3	1.45	E
  446		509.3	1.53	E
  447		481.2	1.38	E
  448		551.2	1.48	E
  449		506.2	2.03	E
  450		530.3	1.52	E
  451		549.3	1.35	E
  452		508.3	1.54	E
  453		480.2	1.98	E
  454		436.3	1.51	E
  455		464.0	1.78	E
  456		506.3	1.68	E
  457		478.0	1.65	E
  458		476.0	1.9	E
  459		476.0	1.77	E
  460		478.0	2.14	E
  461		464.3	1.61	E
  462		547.0	1.45	E
  463		528.0	1.08	F
  464		479.0	0.99	F
  465		493.3	1.03	F
  466		507.3	1.61	E
  467		461.3	1.72	E
  468		504.3	2.18	E
  469		549.3	1.6	E
  470		507.3	1.43	E
  471		549.3	1.61	E
  472		480.3	1.12	F

BIOLOGICAL ASSAYS
• The pharmacological properties of the compounds of this invention may be confirmed by a number of biological assays. The exemplified biological assays, which follow, have been carried out with compounds of the invention.
TLR7/8/9 Inhibition Reporter Assays
• HEK-Blue^™-cells (Invivogen) overexpressing human TLR7, TLR8 or TLR9 receptors were used for screening inhibitors of these receptors using an inducible SEAP (secreted embryonic alkaline phosphatase) reporter gene under the control of the IFN-β minimal promoter fused to five NF-κB and AP-1-binding sites. Briefly, cells are seeded into Greiner 384 well plates (15000 cells per well for TLR7, 20,000 for TLR8 and 25,000 for TLR9) and then treated with test compounds in DMSO to yield a final dose response concentration range of 0.05 nM - 50 µM. After a 30 minute compound pre-treatment at room temperature, the cells are then stimulated with a TLR7 ligand (gardiquimod at a final concentration of 7.5 µM), TLR8 ligand (R848 at a final concentration of 15.9 µM) or TLR9 ligand (ODN2006 at a final concentration of 5 nM) to activate NF-κB and AP-1 which induce the production of SEAP. After a 22 hour incubation at 37 °C, 5% CO₂, SEAP levels are determined with the addition of HEK-Blue^™ Detection reagent (Invivogen), a cell culture medium that allows for detection of SEAP, according to manufacturer's specifications. The percent inhibition is determined as the % reduction in the HEK-Blue signal present in wells treated with agonist plus DMSO alone compared to wells treated with a known inhibitor. TABLE 2

  TLR7/8/9 Reporter Assay Data
  (NT = not tested)
  Ex. No.	TLR7 IC50 (nM)	TLR8 IC50 (nM)	TLR9 IC50 (nM)		Ex. No.	TLR7 IC50 (nM)	TLR8 IC50 (nM)	TLR9 IC50 (nM)
  1	4.7	89	550		234	13	2.6	733
  2	1.6	14	398		235	0.24	1.0	2207
  3	3.2	11	1582		236	0.66	1.1	939
  4	NT	973	13083		237	1.6	0.95	2072
  5	9.5	100	250		238	62	21	28464
  6	0.61	1.4	664		239	2.6	2.6	15894
  7	1.5	0.56	168		240	0.96	0.39	2777
  8	6638	15946	258		241	3.5	11	285
  9	551	8225	26		242	11	14	401
  10	5.6	19	896		243	0.79	4.8	430
  11	1.6	8.3	91		244	8.9	16	583
  12	53	273	866		245	6.3	47	257
  13	6.5	6.8	2783		246	2.0	17	705
  14	3.9	3.4	13016		247	16	10	718
  15	3.5	1.6	13498		248	5.7	6.8	396
  16	4.7	26	1286		249	12	12	1446
  17	1.3	1.6	1861		250	3.2	3.4	4773
  18	0.76	2.6	1790		251	15	23	14850
  19	2.0	3.0	1758		252	6.4	5.2	3360
  20	2.5	4.3	6546		253	0.97	0.77	2859
  21	2.0	2.7	3338		254	1.5	0.55	3011
  22	6.2	1.8	4250		255	0.50	0.49	14492
  23	2.6	3.4	147		256	1.4	1.2	15352
  24	9.7	39	279		257	5.3	6.4	36023
  25	2.3	7.2	188		258	0.77	0.35	6015
  26	3.1	6.9	633		259	2.1	2.6	16752
  27	49	86	477		260	1.4	1.7	837
  28	13	26	608		261	0.61	1.1	1271
  29	4.3	4.7	1696		262	1.3	4.2	1328
  30	4.7	7.7	855		263	1.9	4.1	5654
  31	2.1	6.2	132		264	0.69	0.16	1643
  32	40	124	279		265	0.36	0.42	1025
  33	1.4	6.9	134		266	26	23	2035
  34	2.5	2.0	1506		267	6.9	1.9	16699
  35	1.7	2.8	154		268	4.8	17	757
  36	19	48	208		269	4.4	6.4	205
  37	3.3	4.4	409		270	2.6	3.2	392
  38	2.8	12	13055		271	1.6	4.2	333
  39	6.4	16	5530		272	7.0	22	391
  40	9.9	11	8313		273	8.6	16	376
  41	36	158	>50000		274	42	35	648
  42	1.6	0.59	9177		275	35	37	845
  43	1.0	0.60	12749		276	7.7	1.2	114
  44	0.63	0.36	2766		277	5.5	13	265
  45	2.2	1.9	2766		278	0.79	0.58	1104
  46	0.98	1.6	NT		279	0.65	1.5	1111
  47	5.2	1.5	2580		280	1.3	1.2	2503
  48	12	13	9533		281	16	43	36393
  49	0.46	0.62	2426		282	1.1	0.97	1068
  50	0.76	0.83	1007		283	0.46	0.27	1617
  51	0.74	0.58	2773		284	8.3	14	23513
  52	0.98	0.42	1857		285	1.3	1.6	1868
  53	0.50	2.0	1391		286	2.2	2.2	2858
  54	0.90	0.30	935		287	2.0	16	718
  55	1.3	1.3	769		288	27	8.5	2866
  56	1.8	1.5	1007		289	3.7	58	14030
  57	4.9	19	682		290	20	7.1	>50000
  58	60	23	692		291	3.0	4.9	494
  59	15	4.7	197		292	7.0	47	303
  60	5.0	1.2	502		293	3.1	4.7	29055
  61	28	35	346		294	3.0	4.7	7634
  62	5.1	21	417		296	3.3	5.4	132
  63	11	11	2992		297	>3125	>3125	17861
  64	4.2	1.5	2794		298	14	75	459
  65	2.2	5.6	3318		299	2.9	25	356
  66	2.1	4.9	3623		300	13	1.6	11926
  67	9.1	11	5799		301	>3125	>3125	2681
  68	NT	NT	5289		302	1586	>3125	>50000
  69	0.55	0.55	4053		303	19	12	>50000
  70	0.23	0.78	3998		304	1.5	2.2	505
  71	0.41	0.65	3608		305	2.5	1.4	2829
  72	1.5	1.3	6085		306	3.9	16	786
  73	0.87	0.77	2960		307	3.0	0.85	657
  74	1.7	0.77	694		308	7.9	25	159
  75	2.5	5.6	447		309	7.3	49	133
  76	0.58	3.8	959		310	13	32	640
  77	2.7	4.5	403		312	8.5	114	920
  78	4.3	11	8618		313	2.9	0.27	2416
  79	3.0	3.6	842		314	4.3	1.5	3705
  80	0.16	0.60	1833		315	7.6	47	166
  81	0.15	0.61	2167		316	9.5	33	80
  82	0.18	0.36	1465		317	2.1	7.1	34
  83	1.3	1.4	9103		318	6.0	21	846
  85	2.6	1.1	924		319	12	3.7	14449
  86	0.37	0.43	1127		320	4.4	2.0	3007
  87	0.33	1.0	701		321	2.8	0.64	1009
  88	0.62	0.28	322		322	2.1	0.23	1452
  89	6.5	4.9	435		323	4.5	20	258
  90	20	31	1395		324	3.0	20	283
  91	40	27	676		325	2.4	12	512
  92	34	32	548		326	14	78	1218
  93	18	37	2826		327	7.1	17	771
  95	41	35	1383		328	11	60	1392
  96	24	7.7	294		329	7.5	7.4	647
  97	2.5	7.4	1080		330	1.1	5.5	255
  98	4.7	14	1199		331	263	637	3304
  99	0.49	0.41	3976		332	7.7	56	154
  100	0.80	0.25	2336		333	5.4	4.3	1061
  101	1.2	0.66	4137		334	0.35	1.4	452
  102	0.34	0.24	2824		335	4.3	42	669
  103	0.86	0.48	5916		336	8.8	36	3997
  104	3.6	1.7	5296		337	3.9	4.0	777
  105	0.22	0.59	2249		338	3.4	30	1109
  106	4.9	5.0	1946		339	12	28	677
  107	3.6	4.5	2055		340	1274	708	11475
  108	2.1	4.0	2764		341	3.2	21	1031
  109	0.61	1.7	1665		342	3.8	8.3	224
  110	2.0	1.3	1163		343	28	190	217
  111	1.0	0.48	2999		344	1.7	3.5	257
  112	1.6	2.3	1880		345	11	13	712
  113	0.72	0.57	510		346	3.3	14	750
  114	4.8	6.6	17394		347	3.9	30	790
  115	1.4	2.4	15793		348	3.5	9.0	468
  116	10	42	766		349	1.1	3.6	344
  117	28	41	868		350	1.4	4.7	1082
  118	8.6	1.4	294		351	11	5.4	345
  119	8.1	11	558		352	14	0.73	19800
  120	2.3	2.0	71		353	0.61	1.4	2526
  121	2.7	5.9	759		354	1.6	9.9	3432
  122	14	10	400		355	33	22	5593
  123	26	31	1113		356	15	6.1	18544
  124	0.38	0.65	905		357	21	10	37404
  125	3.1	6.5	7031		358	3.6	3.8	>50000
  126	8.2	3.2	2531		359	2.5	2.7	>50000
  127	47	150	>50000		360	2.9	1.5	23031
  128	1.9	1.4	2477		361	3.8	0.76	4852
  129	0.75	0.15	5903		362	4.9	4.0	NT
  130	1.3	0.76	5250		363	NT	3.7	43685
  131	5.0	7.9	11424		364	2.7	0.38	8704
  132	3.4	5.0	2130		365	0.42	0.51	1490
  133	0.52	1.2	1356		366	3.8	39	16209
  134	0.98	0.27	1025		367	159	52	>50000
  135	0.24	0.48	6501		368	1.3	2.3	5886
  136	0.41	0.32	620		369	27	23	>50000
  137	0.63	0.90	3163		370	19	174	10349
  138	0.26	0.49	1904		371	9.0	5.9	5477
  139	1.1	1.0	1029		372	7.9	440	5441
  140	0.53	1.4	3047		373	8.1	7.1	5815
  141	27	25	482		374	6.0	39	5470
  142	13	39	282		375	17	>3125	7209
  143	33	33	683		376	9.5	>3125	6005
  144	14	14	1252		377	16	16	1413
  145	9.1	11	506		378	6.0	3.4	5108
  146	1.1	0.46	6659		379	4.0	2.3	3632
  147	0.62	0.27	2059		380	5.6	7.8	1479
  148	1.1	1.7	1171		381	9.9	11	2579
  149	3.6	5.1	13082		382	4.5	18	>50000
  150	3.4	5.3	6057		383	2.7	0.31	5394
  151	1.1	4.4	768		384	0.96	0.55	3263
  152	5.0	6.4	4090		385	4.1	1.4	42122
  153	8.8	5.2	3826		386	26	6.8	>50000
  154	4.0	4.4	1225		387	33	13	>50000
  155	7.3	5.0	6312		388	2.7	0.81	1892
  156	0.79	0.26	6429		389	1.1	0.38	6162
  157	0.80	0.51	4178		390	2.3	0.15	4062
  158	1.4	2.1	17503		391	1.4	0.90	4046
  159	3.4	4.5	455		392	24	13	8839
  160	0.56	0.57	1279		393	1.4	0.51	8732
  161	2.4	4.6	293		394	1.6	1.0	13706
  162	1.3	1.0	2152		395	44	6.6	17520
  163	0.39	0.87	1321		396	99	19	>50000
  164	6.2	4.6	1800		397	48	30	43179
  165	0.40	0.62	905		398	7.2	1.9	46809
  166	0.41	0.18	3343		399	409	4.1	>50000
  167	2.6	0.49	4329		400	82	1.6	>50000
  168	3.6	4.5	17459		401	27	4.4	6437
  169	0.36	0.33	1731		402	30	4.4	5969
  170	0.42	0.71	2291		403	25	1.7	9265
  171	0.43	0.12	1964		404	32	4.0	5807
  172	4.4	0.75	2652		405	46	15	17055
  173	1.5	0.54	653		406	8.4	4.8	937
  174	0.78	0.67	7716		407	47	828	35363
  175	23	6.4	7938		408	16	61	12421
  176	16	18	325		409	2.5	3.4	>50000
  177	8.7	4.0	549		410	15	1.3	>50000
  178	7.0	2.7	321		411	9.6	0.18	11154
  179	20	7.0	486		412	6.7	0.29	5739
  180	1.3	9.6	664		413	29	6.1	>50000
  181	1.5	5.0	6552		414	41	6.2	>50000
  182	3.8	11	18769		415	26	5.2	>50000
  183	1.8	3.4	2446		416	10	1.7	1729
  184	1.9	7.9	1871		417	16	13	>50000
  185	6.2	7.8	1553		418	19	2.2	6014
  186	12	6.6	26512		419	32	1.4	5905
  187	2.1	2.0	1526		421	16	12	>50000
  188	1.6	0.21	5163		422	3.1	2.0	6817
  189	20	16	30736		423	5.4	0.59	42520
  190	0.77	0.22	874		424	6.3	0.39	17690
  191	0.91	1.1	3501		425	13	17	>50000
  192	5.3	3.9	3143		426	30	0.54	>50000
  193	0.84	0.40	1252		427	35	37	>50000
  194	5.3	2.6	575		428	12	1.1	39542
  195	5.2	3.0	577		429	9.3	2.3	>50000
  196	3.0	1.1	2079		430	5.9	0.27	6111
  197	0.30	0.44	1572		431	3.5	0.32	8176
  198	2.4	2.6	1151		432	102	2.7	>50000
  199	0.83	2.0	1211		433	3.0	0.32	6914
  200	3.0	1.1	8782		434	90	48	>50000
  201	0.49	0.52	1788		436	1.8	5.1	10338
  202	0.35	1.2	2459		437	2.6	6.4	7666
  203	27	9.3	513		438	25	13	>50000
  204	6.6	3.1	466		439	7.1	4.3	11236
  205	1.2	0.55	600		440	11	62	>50000
  206	9.2	13	260		441	4.0	11	7321
  207	5.3	7.7	437		442	2.5	7.1	7489
  208	12	16	276		443	4.0	9.3	6551
  209	29	97	1078		444	5.0	6.7	19901
  210	34	6.6	1080		445	13	25	>50000
  211	41	44	2253		446	18	21	>50000
  212	1.6	3.8	2082		447	11	32	>50000
  213	1.5	3.0	517		448	28	22	>50000
  214	7.5	16	2071		449	37	171	>50000
  215	4.2	3.7	1996		450	12	39	>50000
  216	14	12	4647		451	2.6	5.7	792
  217	3.4	4.4	7599		452	4.8	11	12564
  218	0.82	0.60	4744		453	16	34	>50000
  219	0.85	0.56	1893		454	0.05	0.05	10860
  220	0.74	0.35	4536		455	0.59	0.17	14561
  221	1.1	0.70	2574		456	5.7	1.6	16284
  222	3.2	2.7	5774		457	3.2	2.5	21953
  223	2.7	2.4	1110		458	2.5	1.2	16792
  224	0.40	0.62	679		459	1.6	0.54	13834
  225	4.0	1.4	4699		460	10	4.4	>50000
  226	0.51	0.73	1292		461	5.4	1.5	9015
  227	1.9	2.6	4322		462	1.1	1.5	1974
  228	1.5	2.6	812		463	9.0	5.2	38772
  229	8.7	4.2	1458		464	7.3	2.6	43951
  230	0.41	0.77	1703		465	8.5	3.1	47913
  231	5.9	6.6	4167		466	16	2.5	47526
  232	11	3.2	4496		467	2.8	1.4	17054
  233	2.7	3.6	1161		468	43	50	>50000
  234	13	2.6	733		469	13	3.5	47935
  235	0.24	1.0	2207		470	4.9	0.49	15491
  236	0.66	1.1	939		471	27	2.7	>50000
  237	1.6	0.95	2072		472	5.3	0.92	46640

Claims (8)

1. A compound of Formula (I)

   

   N-oxide, stereoisomers, tautomers, solvates or a pharmaceutically-acceptable salt thereof, wherein: G is:

   

   A is:

   (i) -NR₇R₈ wherein R₇ and R₈ together with the nitrogen atom to which they are attached form a heterocyclic ring selected from piperazinyl, piperidinyl, or diazaspiro[3.3]heptanyl, wherein said heterocyclic ring is substituted with zero to 1 R_7b and zero to 1 R_7c; or

   (ii) -CHR₁₂R₁₃, wherein R₁₂ and R₁₃ together with the carbon atom to which they are attached form a cyclic group selected from cyclopentyl, cyclohexyl, morpholinyl, or piperidinyl, each substituted with zero to 1 R_12a;

   R₁ is -CH(CH₃)₂;

   each R₂ is independently-CH₃ or -OCH₃;

   R₅ is F, Cl, or -CH₃;

   R_7b is:

   (i) -CH₃, -CH₂CH₃, -CH₂CH₂CH₃, -CH(CH₃)₂, -CH₂CH(CH₃)₂, -CH₂CF₃, -CH₂CN, -CH₂C(CH₃)₂OH, -CH₂CH₂OCH₃, -CH₂CH₂S(O)₂CH₃, -(CH₂)_1-2NR_xR_x, -CH₂C(O)NR_xR_x, -NR_xR_y, -NR_x(C_1-4 hydroxyalkyl), -NH(CH₂CR_xR_xOCH₃), -NR_y(C_1-2 cyanoalkyl), -NR_x(C_1-2 fluoroalkyl), -NR_x(C_2-5 hydroxyfluoroalkyl), -NR_x(CH₂)_1-2C(O)NR_xR_x, -NR_x(CH₂)_1-3NR_xR_x, -NR_xCH₂CH₂N(CH₃)₂, -NR_xC(O)(CH₂)_1-2NR_xR_x, -C(O)CH₃, -C(O)CH₂NR_xR_x, -S(O)₂CH₃, -(CH₂)_1-2R_7d, -CH₂C(O)R_7d, -C(O)CH₂R_7d, -NHR_7d, -NH(CH₂)_1-2R_7d, or -OR_7d; or

   (ii) azetidinyl, cyclobutyl, dioxothiomorpholinyl, morpholinyl, oxaazaspiro[3.3]heptanyl, oxetanyl, piperazinonyl, piperazinyl, piperidinyl, tetrahydrofuranyl, or tetrahydropyranyl, each substituted with zero to 1 R_8a;

   R7c is -CH₃;

   R_7d is azaspiro[3.5]nonanyl, bicyclo[1.1.1]pentanyl, C_3-6 cycloalkyl, morpholinyl, oxetanyl, phenyl, piperidinyl, pyrazolyl, pyrrolidinyl, tetrahydrofuranyl, or tetrahydropyranyl, each substituted with zero to 1 substituent selected from C_1-3 alkyl, -NR_xR_x, -C(O)CH₃, methylpiperidinyl, methylpyrrolidinyl, tetramethylpiperidinyl, -OCH₂CH₂(pyrrolidinyl), and -OCH₂CH₂NHCH₂CH₃; and zero to 4 substituents selected from -CH₃;

   R_8a is -CH₃, -CH(CH₃)₂, or -S(O)₂CH₃;

   R12a is -CH(CH₃)₂, -CH₂CF₃, -CH₂C(CH₃)₂OH, -CH₂CH₂OCH₃, -CH2C(O)NH(CH3), -CH₂C(O)N(CH₃)₂, -CH₂C(O)NH₂, -CH₂CH₂S(O)₂CH₃, -CH₂CH₂NH(CH₃), -NR_xR_y, -NR_x(C_2-4 fluoroalkyl), -NH(CH₂C(CH₃)₂OH), -NH(CH₂CHFC(CH₃)₂OH), -NH(CH₂CH₂OCH₃), -NH(CH₂C(CH₃)₂OCH₃), -NR_x(CH₂C(O)NR_xR_x), -C(O)CH₂NH(CH₃), -C(O)CH₂N(CH₃)₂, R_12b, -CH₂R_12b, -NR_xR_12b, -N(CH₂CN)R_12b, or -NR_xCH₂R_12b;

   R_12b is azetidinyl, bicyclo[1.1.1]pentanyl, oxaazaspiro[3.3]heptanyl, oxetanyl, piperidinyl, tetrahydrofuranyl, or tetrahydropyranyl, each substituted with zero to 4 substituents independently selected from -CH₃, -CH(CH₃)₂, -CH₂OH, or -OCH₃;

   each R_x is independently H or -CH₃;

   p is zero, 1, 2, 3, or 4 and

   n is zero or 1.
2. The compound according to claim 1, N-oxide, stereoisomers, tautomers, solvates or a pharmaceutically-acceptable salt thereof, wherein:

   G is:

   

   A is: -NR₇R₈ wherein R₇ and R₈ together with the nitrogen atom to which they are attached form a heterocyclic ring selected from piperazinyl, piperidinyl, or diazaspiro[3.3]heptanyl, wherein said heterocyclic ring is substituted with zero to 1 R_7b and zero to 1 R_7c; or

   R₁ is -CH(CH₃)₂;

   each R₂ is independently-CH₃ or -OCH₃;

   R₅ is F, Cl, or -CH₃;

   R_7b is:

   (i) -CH₃, -CH₂CH₃, -CH₂CH₂CH₃, -CH(CH₃)₂, -CH₂CH(CH₃)₂, -CH₂CF₃, -CH₂CN, -CH₂C(CH₃)₂OH, -CH₂CH₂OCH₃, -CH₂CH₂S(O)₂CH₃, -(CH₂)_1-2NR_xR_x, -CH₂C(O)NR_xR_x, -NR_xR_y, -NR_x(C_1-4 hydroxyalkyl), -NH(CH₂CR_xR_xOCH₃), -NR_y(C_1-2 cyanoalkyl), -NR_x(C_1-2 fluoroalkyl), -NR_x(C_2-5 hydroxyfluoroalkyl), -NR_x(CH₂)_1-2C(O)NR_xR_x, -NR_x(CH₂)_1-3NR_xR_x, -NR_xCH₂CH₂N(CH₃)₂, -NR_xC(O)(CH₂)_1-2NR_xR_x, -C(O)CH₃, -C(O)CH₂NR_xR_x, -S(O)₂CH₃, -(CH₂)_1-2R_7d, -CH₂C(O)R_7d, -C(O)CH₂R_7d, -NHR_7d, -NH(CH₂)_1-2R_7d, or -OR_7d; or

   (ii) azetidinyl, bicyclo[1.1.1]pentanyl, cyclobutyl, dioxothiomorpholinyl, morpholinyl, oxaazaspiro[3.3]heptanyl, oxetanyl, piperazinonyl, piperazinyl, piperidinyl, tetrahydrofuranyl, or tetrahydropyranyl, each substituted with zero to 1 R_8a;

   R7c is -CH₃;

   R_8a is -CH₃, -CH(CH₃)₂, or -S(O)₂CH₃;

   and n is zero or 1.
3. The compound according to claim 1, N-oxide, stereoisomers, tautomers, solvates or a pharmaceutically-acceptable salt thereof, wherein:

   G is:

   

   A is: -CHR₁₂R₁₃, wherein R₁₂ and R₁₃ together with the carbon atom to which they are attached form a cyclic group selected from cyclopentyl, cyclohexyl, morpholinyl, or piperidinyl, each substituted with zero to 1 R_12a;

   R₁ is -CH(CH₃)₂;

   each R₂ is independently-CH₃ or -OCH₃;

   R₅ is F, Cl, or -CH₃;

   R12a is -CH(CH₃)₂, -CH₂CF₃, -CH₂C(CH₃)₂OH, -CH₂CH₂OCH₃, -CH2C(O)NH(CH3), -CH₂C(O)N(CH₃)₂, -CH₂C(O)NH₂, -CH₂CH₂S(O)₂CH₃, -CH₂CH₂NH(CH₃), -NR_xR_y, -NR_x(C_2-4 fluoroalkyl), -NH(CH₂C(CH₃)₂OH), -NH(CH₂CHFC(CH₃)₂OH), -NH(CH₂CH₂OCH₃), -NH(CH₂C(CH₃)₂OCH₃), -NR_x(CH₂C(O)NR_xR_x), -C(O)CH₂NH(CH₃), -C(O)CH₂N(CH₃)₂, R_12b, -CH₂R_12b, -NR_xR_12b, -N(CH₂CN)R_12b, or -NR_xCH₂R_12b;

   R_12b is azetidinyl, bicyclo[1.1.1]pentanyl, oxaazaspiro[3.3]heptanyl, oxetanyl, piperidinyl, tetrahydrofuranyl, or tetrahydropyranyl, each substituted with zero to 4 substituents independently selected from -CH₃, -CH(CH₃)₂, -CH₂OH, or -OCH₃;

   and n is zero or 1.
4. The compound according to claim 1, N-oxide, stereoisomers, tautomers, solvates or a pharmaceutically-acceptable salt thereof, wherein said compound is 6-(3-isopropyl-4-methyl-5-(piperidin-4-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4] triazolo[1,5-a]pyridine (1); 2-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidin-1-yl)-N-methylacetamide (2); 6-(4-fluoro-3-isopropyl-5-(piperidin-4-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (3); 6-(3-isopropyl-5-(piperidin-4-yl)-1h-pyrrolo[2,3-c]pyridin-2-yl)-8-methyl-[1,2,4]triazolo [1,5-a]pyridine (4); 2-(dimethylamino)-1-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a] pyridine-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidin-1-yl)ethan-1-one (5); 6-(4-chloro-3-isopropyl-5-(piperazin-1-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (6); 6-(3-isopropyl-5-(piperazin-1-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo [1,5-a]pyridine (7, 295); 1-(4-(4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidin-1-yl)-2-(methylamino)ethan-1-one (10); 2-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidin-1-yl)acetamide (11); 1-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidin-1-yl)-2-(methylamino)ethan-1-one (12); 6-(4-fluoro-3-isopropyl-5-(piperidin-4-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (13); 6-(4-fluoro-3-isopropyl-5-(1-(2-(methylsulfonyl)ethyl)piperidin-4-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (14); 2-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidin-1-yl)acetamide (15); 6-(3-isopropyl-4-methyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (16); 6-(4-fluoro-3-isopropyl-5-(1-((3-methyloxetan-3-yl)methyl)piperidin-4-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (17); 6-(4-fluoro-3-isopropyl-5-(1-isopropylpiperidin-4-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (18); 2-(4-(4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidin-1-yl) acetamide (19); 2-(4-(4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidin-1-yl)-N-methylacetamide (20); 6-(4-fluoro-3-isopropyl-5-(1-(2-methoxyethyl)piperidin-4-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (21); 2-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a] pyridin-6-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidin-1-yl)-N,N-dimethylacetamide (22); 2-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidin-1-yl)acetamide (23); 2-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-methyl-1H-pyrrolo[2,3-c] pyridin-5-yl)piperidin-1-yl)-N,N-dimethylacetamide (24); 6-(3-isopropyl-4-methyl-5-(1-(2-(methylsulfonyl)ethyl)piperidin-4-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (25); 2-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidin-1-yl)-N-methylacetamide (26); 2-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[2,3-c] pyridin-5-yl)piperidin-1-yl)-N-methylacetamide (27); 6-(3-isopropyl-5-(piperidin-4-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (28); 1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidin-1-yl)-2-(dimethylamino)ethan-1-one (29); 6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine(30);2-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidin-1-yl)-N,N-dimethylacetamide (31); 2-(dimethylamino)-1-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidin-1-yl)ethan-1-one (32); 6-(3-isopropyl-5-(1-isopropylpiperidin-4-yl)-4-methyl-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (33); 2-(4-(4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidin-1-yl)-N,N-dimethylacetamide (34); 6-(3-isopropyl-5-(1-isopropylpiperidin-4-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (35); 1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidin-1-yl)-2-(dimethylamino)ethan-1-one (36); 2-(dimethylamino)-1-(4-(4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidin-1-yl)ethan-1-one (37); 6-(4-fluoro-3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (38); 1-(4-(4-fluoro-3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidin-1-yl)-2-(methylamino)ethan-1-one (39); 2-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl)piperazin-1-yl)-N-methylacetamide (40); 6-(4-fluoro-3-isopropyl-5-(1-(2,2,2-trifluoroethyl)piperidin-4-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine (41); 1-(4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c] pyridin-5-yl)-N-(oxetan-3-yl)piperidin-4-amine (42); 1-(4-fluoro-3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-(3-methyloxetan-3-yl)piperidin-4-amine (43); 6-(1-(4-fluoro-3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidin-4-yl)-2-oxa-6-azaspiro[3.3]heptane (44); 2-((1-(4-fluoro-3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidin-4-yl)(methyl)amino)-N,N-dimethylacetamide (45); 6-(5-(4-(azetidin-1-yl)cyclohexyl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (46, 75); 1-(4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c] pyridin-5-yl)-N-methyl-N-neopentylpiperidin-4-amine (47); 4-(4-fluoro-3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-neopentylcyclohexan-1-amine (48, 260); 1-((4-(4-fluoro-3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)cyclohexyl)amino)-2-methylpropan-2-ol (49, 164); 6-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-5-yl)cyclohexyl)-2-oxa-6-azaspiro[3.3]heptane (50); 6-(5-(4-(azetidin-1-yl)piperidin-1-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (51); 1-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-isopropyl-N-methylpiperidin-4-amine (52); 6-(1-(3-isopropyl-4-methyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidin-4-yl)-2-oxa-6-azaspiro[3.3]heptane (53); 1-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-4-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-((3-methyloxetan-3-yl)methyl)piperidin-4-amine (54); 1-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-4-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-ethyl-N-methylpiperidin-4-amine (55); N-(bicyclo[1.1.1]pentan-1-yl)-1-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidin-4-amine (56); 6-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-4-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl)cyclohexyl)-2-oxa-6-azaspiro[3.3]heptane (57, 142); 4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-4-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-neopentylcyclohexan-1-amine (58, 247); 3-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c] pyridin-5-yl)-N-((3-methyloxetan-3-yl)methyl)cyclopentan-1-amine (59, 94, 275-276); 3-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-neopentylcyclopentan-1-amine (60, 95, 144, 210); 4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-4-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-isopropylcyclohexan-1-amine (61, 277); 6-(3-isopropyl-5-(4-(3-methoxyazetidin-1-yl)cyclohexyl)-4-methyl-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a] pyridine (62, 180); N-isopropyl-3-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a] pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-methylcyclopentan-1-amine (63, 145); (R)-3-fluoro-4-((1-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidin-4-yl)amino)-2-methylbutan-2-ol (64); 2-(dimethylamino)-1-(4-(4-fluoro-3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidin-1-yl)ethan-1-one (65); 2-(dimethylamino)-1-(4-(4-fluoro-3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidin-1-yl)ethan-1-one (66); 1-(4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-((3-methyloxetan-3-yl)methyl)piperidin-4-amine (67); 1-(4-fluoro-3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-isopropyl-N-methylpiperidin-4-amine (68); N-ethyl-1-(4-fluoro-3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-methylpiperidin-4-amine (69); 6-(5-(4-(azetidin-1-yl)piperidin-1-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine (70); 1-(4-fluoro-3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-methylpiperidin-4-amine (71); 2-((1-(4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidin-4-yl)(methyl)amino)-N,N-dimethylacetamide (72); 4-(4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-isopropylcyclohexan-1-amine (73, 159); 1-((4-(4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)cyclohexyl)amino)-2-methylpropan-2-ol (74, 195); 4-(4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-isopropyl-N-methylcyclohexan-1-amine (76, 227); N-ethyl-4-(4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a] pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-methylcyclohexan-1-amine (77, 228); 2-((4-(4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)cyclohexyl)(methyl)amino)acetamide (78); 2-((4-(4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)cyclohexyl)(methyl)amino)-N,N-dimethylacetamide (79, 131); N-(4-(4-fluoro-3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl) cyclohexyl)oxetan-3-amine (80); N-(4-(4-fluoro-3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)cyclohexyl)-3-methyloxetan-3-amine (81, 105, 192); N-(4-(4-fluoro-3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)cyclohexyl)tetrahydro-2H-pyran-4-amine (82, 110); 1-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-ethyl-N-methylpiperidin-4-amine (83); 4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-isopropyl-N-methylcyclohexan-1-amine (84); 4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c] pyridin-5-yl)-N-isopropylcyclohexan-1-amine (85, 136); N-isopropyl-1-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-methylpiperidin-4-amine (86); 6-(5-(4-(azetidin-1-yl)piperidin-1-yl)-3-isopropyl-4-methyl-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (87); 1-((1-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-4-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidin-4-yl)amino)-2-methylpropan-2-ol (88); (R)-3-fluoro-4-((4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl)cyclohexyl)amino)-2-methylbutan-2-ol (89, 117); 4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-4-methyl-1H-pyrrolo[2,3-c] pyridin-5-yl)-N-ethyl-N-methylcyclohexan-1-amine (90); N-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-4-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl) cyclohexyl)oxetan-3-amine (91, 121); 1-((4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a] pyridin-6-yl)-3-isopropyl-4-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl)cyclohexyl)amino)-2-methylpropan-2-ol (92, 122); N-(3-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a] pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)cyclopentyl)oxetan-3-amine (93, 178, 273-274); 3-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c] pyridin-5-yl)-N-(2-methoxy-2-methylpropyl)cyclopentan-1-amine (96, 123, 179); 2-(2,6-dimethylpyridin-4-yl)-4-fluoro-3-isopropyl-5-(1-isopropylpiperidin-4-yl)-1H-pyrrolo[2,3-c]pyridine (97); 1-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a] pyridin-6-yl)-4-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl)piperazin-1-yl)-2-(methylamino) ethan-1-one (98); 1-(4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-(2-methoxyethyl)piperidin-4-amine (99); 1-(4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c] pyridin-5-yl)-N-(tetrahydro-2H-pyran-4-yl)piperidin-4-amine (100); 1-(4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-isopropyl-N-methylpiperidin-4-amine (101); N-ethyl-1-(4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-methylpiperidin-4-amine (102); 1-(4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-(tetrahydrofuran-3-yl)piperidin-4-amine (103, 190); 1-(4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-methyl-N-(oxetan-3-yl)piperidin-4-amine (104); N-(4-(4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)cyclohexyl)-N-methyloxetan-3-amine (106, 197); N-(4-(4-fluoro-3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)cyclohexyl)oxetan-3-amine (107); 4-(4-fluoro-3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-isopropyl-N-methylcyclohexan-1-amine (108, 261); 6-(5-(4-(azetidin-1-yl) cyclohexyl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine (109, 262); 6-(1-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a] pyridin-6-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidin-4-yl)-2-oxa-6-azaspiro[3.3]heptane (111); 1-(3-isopropyl-4-methyl-2-(8-methyl-[1,2,4]triazolo[1,5-a ]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-neopentylpiperidin-4-amine (112); 1-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-4-methyl-1H-pyrrolo[2,3-c] pyridin-5-yl)-N-isopropylpiperidin-4-amine (113); 2-((4-(4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)cyclohexyl) (oxetan-3-yl)amino)acetonitrile (114-115); N-ethyl-4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-methylcyclohexan-1-amine (116, 268); 6-(3-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)cyclopentyl)-2-oxa-6-azaspiro[3.3]heptane (118, 141, 208-209); N-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a] pyridin-6-yl)-3-isopropyl-4-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl)cyclohexyl)tetrahydro-2H-pyran-4-amine (119); N-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-4-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl)cyclohexyl)tetrahydro-2H-pyran-4-amine (120); N-isopropyl-1-(3-isopropyl-4-methyl-2-(8-methyl-[1,2,4]triazolo[1,5-a] pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-methylpiperidin-4-amine (124); 2-(4-(4-fluoro-3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c] pyridin-5-yl)piperidin-1-yl)acetamide (125); 6-(3-isopropyl-5-(4-(2-methoxyethyl)piperazin-1-yl)-4-methyl-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (126); 6-(4-fluoro-3-isopropyl-5-(1-(2,2,2-trifluoroethyl) piperidin-4-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (127); 1-(4-(4-fluoro-3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidin-1-yl)-2-methylpropan-2-ol (128); 1-(4-fluoro-3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-((3-methyloxetan-3-yl)methyl)piperidin-4-amine (129); 1-(4-fluoro-3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-methyl-N-(oxetan-3-yl)piperidin-4-amine (130); 6-(4-(4-fluoro-3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)cyclohexyl)-2-oxa-6-azaspiro[3.3]heptane (132-133); N-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-5-yl)cyclohexyl)tetrahydro-2H-pyran-4-amine (134, 232); 4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-ethyl-N-methylcyclohexan-1-amine (135, 263); 1-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-(oxetan-3-yl)piperidin-4-amine (137); N-ethyl-1-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-methyl-1H-pyrrolo[2,3-c] pyridin-5-yl)-N-methylpiperidin-4-amine (138); 6-(1-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidin-4-yl)-2-oxa-6-azaspiro[3.3]heptane (139); 1-(3-isopropyl-4-methyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-(oxetan-3-yl) piperidin-4-amine (140); 1-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-(oxetan-3-yl)piperidin-4-amine (146); 1-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-((3-methyloxetan-3-yl)methyl)piperidin-4-amine (147); N-(bicyclo[1.1.1]pentan-1-yl)-1-(3-isopropyl-4-methyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidin-4-amine (148); 6-(4-fluoro-3-isopropyl-5-(1-(2-(methylsulfonyl)ethyl)piperidin-4-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine (149); 2-(4-(2-(2,6-dimethylpyridin-4-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidin-1-yl)-N-methylacetamide (150); 2-(2,6-dimethylpyridin-4-yl)-4-fluoro-3-isopropyl-5-(piperidin-4-yl)-1H-pyrrolo[2,3-c]pyridine (151); 2-(4-(2-(2,6-dimethylpyridin-4-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidin-1-yl)acetamide (152); 2-(4-(2-(2,6-dimethylpyridin-4-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidin-1-yl)-N,N-dimethylacetamide (153); 2-(dimethylamino)-1-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl)piperazin-1-yl)ethan-1-one (154); 2-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl)piperazin-1-yl)acetamide (155); 1-((1-(4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidin-4-yl)amino)-2-methylpropan-2-ol (156); 1-(4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-isopropylpiperidin-4-amine (157); 2-((1-(4-fluoro-3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidin-4-yl)(methyl) amino)acetamide (158); N-(4-(4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a] pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)cyclohexyl)tetrahydro-2H-pyran-4-amine (160, 194); 6-(4-(4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)cyclohexyl)-2-oxa-6-azaspiro[3.3]heptane (161, 226); 4-(4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c] pyridin-5-yl)-N-neopentylcyclohexan-1-amine (162, 229); N-ethyl-4-(4-fluoro-3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-methylcyclohexan-1-amine (163, 199); 6-(5-(4-(azetidin-1-yl)cyclohexyl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (165, 233); 1-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-isopropylpiperidin-4-amine (166); 1-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-neopentylpiperidin-4-amine (167); 4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-isopropyl-N-methylcyclohexan-1-amine (168); 1-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a] pyridin-6-yl)-4-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-neopentylpiperidin-4-amine (169); 1-(3-isopropyl-4-methyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-((3-methyloxetan-3-yl)methyl)piperidin-4-amine (170); 4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-((3-methyloxetan-3-yl)methyl)cyclohexan-1-amine (171-172); 1-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-4-methyl-1H-pyrrolo[2,3-c] pyridin-5-yl)-N-(2-methoxy-2-methylpropyl)piperidin-4-amine (173); N-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c] pyridin-5-yl)cyclohexyl)oxetan-3-amine (174, 267); (R)-4-((4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-5-yl)cyclohexyl)amino)-3-fluoro-2-methylbutan-2-ol (175, 240); N-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl) cyclohexyl)tetrahydro-2H-pyran-4-amine (176); N-ethyl-3-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-methylcyclopentan-1-amine (177, 248-249, 272); 2-(4-(4-fluoro-3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidin-1-yl)-N-methylacetamide (181); 6-(4-fluoro-3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine (182); 6-(4-fluoro-3-isopropyl-5-(1-(2-methoxyethyl)piperidin-4-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine (183); 6-(4-fluoro-3-isopropyl-5-(piperidin-4-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine (184); 2-(dimethylamino)-1-(4-(2-(2,6-dimethylpyridin-4-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidin-1-yl)ethan-1-one (185); 6-(3-isopropyl-4-methyl-5-(4-(2-(methylsulfonyl)ethyl)piperazin-1-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (186); 6-(4-fluoro-3-isopropyl-5-(1-(tetrahydro-2H-pyran-4-yl)piperidin-4-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a] pyridine (187); 1-(4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-(3-methyloxetan-3-yl)piperidin-4-amine (188); N-(2,2-difluoroethyl)-1-(4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-methylpiperidin-4-amine (189); 1-(4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-methylpiperidin-4-amine (191); 4-(4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-((3-methyloxetan-3-yl)methyl)cyclohexan-1-amine (193, 225); 1-(4-fluoro-3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-methyl-N-neopentylpiperidin-4-amine (196); 4-(4-fluoro-3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-isopropylcyclohexan-1-amine (198, 230); 4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a] pyridin-6-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-neopentylcyclohexan-1-amine (200, 234); 1-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-(tetrahydro-2H-pyran-4-yl)piperidin-4-amine (201); N-isopropyl-1-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl) piperidin-4-amine (202); 4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-4-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-((3-methyloxetan-3-yl)methyl) cyclohexan-1-amine (203-204); 1-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-4-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-(tetrahydro-2H-pyran-4-yl) piperidin-4-amine (205); 4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-(2-methoxy-2-methylpropyl)cyclohexan-1-amine (206-207); 3-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-(2-methoxy-2-methylpropyl)cyclopentan-1-amine (211); 6-(4-fluoro-3-isopropyl-5-(1-isopropylpiperidin-4-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine (212); 1-(4-(2-(2,6-dimethylpyridin-4-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidin-1-yl)-2-(methylamino)ethan-1-one (214); 2-(2,6-dimethylpyridin-4-yl)-4-fluoro-3-isopropyl-5-(1-((3-methyloxetan-3-yl) methyl)piperidin-4-yl)-1H-pyrrolo[2,3-c]pyridine (215); 2-(2,6-dimethylpyridin-4-yl)-4-fluoro-3-isopropyl-5-(1-(2-methoxyethyl)piperidin-4-yl)-1H-pyrrolo[2,3-c]pyridine (216); 6-(4-fluoro-3-isopropyl-5-(1-(tetrahydro-2H-pyran-4-yl)piperidin-4-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (217); 1-(4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-N,N-dimethylpiperidin-4-amine (218); 1-(4-fluoro-3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-isopropylpiperidin-4-amine (219); 1-(4-fluoro-3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-(tetrahydro-2H-pyran-4-yl)piperidin-4-amine (220); 2-((1-(4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidin-4-yl)(methyl)amino)-N-methylacetamide (221); 2-((1-(4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidin-4-yl)(methyl)amino)acetamide (222); N-(4-(4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)cyclohexyl)oxetan-3-amine (223-224); N-(4-(4-fluoro-3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)cyclohexyl)-3-methyloxetan-3-amine (231); N-ethyl-1-(3-isopropyl-4-methyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-methylpiperidin-4-amine (235); N-isopropyl-1-(3-isopropyl-4-methyl-2-(8-methyl-[1,2,4]triazolo[1,5-a] pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidin-4-amine (236); 1-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-4-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-(oxetan-3-yl)piperidin-4-amine (237); N-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-5-yl)cyclohexyl) bicyclo[1.1.1]pentan-1-amine (238-239); N-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl)cyclohexyl)tetrahydro-2H-pyran-4-amine (241); N-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl) cyclohexyl)oxetan-3-amine (242-243); N-(2-fluoro-2-methylpropyl)-4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl) cyclohexan-1-amine (244, 271); 6-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a] pyridin-6-yl)-4-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl)cyclohexyl)-2-oxa-6-azaspiro[3.3]heptane (245-246); 6-(4-fluoro-3-isopropyl-5-(1-((3-methyloxetan-3-yl) methyl)piperidin-4-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a] pyridine (250); 2-(2,6-dimethylpyridin-4-yl)-4-fluoro-3-isopropyl-5-(1-(oxetan-3-yl) piperidin-4-yl)-1H-pyrrolo[2,3-c]pyridine (251); 2-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl)piperazin-1-yl)-N,N-dimethylacetamide (252); 6-(5-(4-(azetidin-1-yl)piperidin-1-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (253); 6-(1-(4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidin-4-yl)-2-oxa-6-azaspiro[3.3]heptane (254); 1-(4-fluoro-3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c] pyridin-5-yl)-N-(oxetan-3-yl)piperidin-4-amine (255); 1-(4-fluoro-3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-N,N-dimethylpiperidin-4-amine (256); N-(2,2-difluoroethyl)-1-(4-fluoro-3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-methylpiperidin-4-amine (257); 1-((1-(4-fluoro-3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidin-4-yl)amino)-2-methylpropan-2-ol (258); 2-((1-(4-fluoro-3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidin-4-yl)(methyl)amino)-N-methylacetamide (259); 1-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-(tetrahydro-2H-pyran-4-yl)piperidin-4-amine (264); 1-(3-isopropyl-4-methyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-(tetrahydro-2H-pyran-4-yl)piperidin-4-amine (265); (1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-5-yl)cyclohexyl)azetidine-3,3-diyl)dimethanol (266); 4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-((3-methyloxetan-3-yl)methyl)cyclohexan-1-amine (269-270); 4-(1-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl) piperidin-4-yl)morpholine (278); 6-(5-(4-(azetidin-1-yl)piperidin-1-yl)-3-isopropyl-4-methyl-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine (279); 3-((1-(3-isopropyl-4-methyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidin-4-yl)(methyl)amino)propanenitrile (280); 4-(1-(3-isopropyl-4-methyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c] pyridin-5-yl)piperidin-4-yl)thiomorpholine 1,1-dioxide (281); 4-(1-(3-isopropyl-4-methyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl) piperidin-4-yl)morpholine (282); 1-((1-(3-isopropyl-4-methyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidin-4-yl)amino)-2-methylpropan-2-ol (283); 4-(1-(3-isopropyl-4-methyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidin-4-yl)piperazin-2-one (284); 6-(3-isopropyl-4-methyl-5-(4-(4-(methylsulfonyl)piperazin-1-yl)piperidin-1-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine (285); 3-(ethyl(1-(3-isopropyl-4-methyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c] pyridin-5-yl)piperidin-4-yl)amino)propanenitrile (286); 2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidin-1-yl)-N-methylacetamide (287); 2-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperazin-1-yl)-N-methylacetamide (288); 1-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperazin-1-yl)-2-(methylamino)ethan-1-one (289); 6-(3-isopropyl-5-(4-(2-(methylsulfonyl)ethyl)piperazin-1-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (290); 1-(4-(4-chloro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperazin-1-yl)-2-(methylamino)ethan-1-one (291); 2-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a] pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidin-1-yl)-N-methylacetamide (292); 2-(4-(4-chloro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperazin-1-yl)-N-methylacetamide (293); 6-(4-chloro-3-isopropyl-5-(4-(2-(methylsulfonyl)ethyl)piperazin-1-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (294); 1-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidin-1-yl)-2-methylpropan-2-ol (296); 2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperazin-1-yl)-N,N-dimethylacetamide (297, 302); 2-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c] pyridin-5-yl)piperidin-1-yl)-N,N-dimethylacetamide (298); 2-(4-(3-isopropyl-2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidin-1-yl)-N,N-dimethylacetamide (299); 2-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a] pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperazin-1-yl)-N,N-dimethylacetamide (300); 6-(3-isopropyl-5-(piperazin-1-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine (301); 6-(3-isopropyl-5-(4-(oxetan-3-yl)piperazin-1-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (303); 1-(4-(4-chloro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c] pyridin-5-yl)piperazin-1-yl)-2-(dimethylamino)ethan-1-one (304); 2-(4-(4-chloro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperazin-1-yl)-N,N-dimethylacetamide (305); 6-(3-isopropyl-5-(1-(oxetan-3-yl) piperidin-4-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (306); N-isopropyl-1-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidin-4-amine (307); N-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)cyclohexyl)oxetan-3-amine (308, 330); 6-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)cyclohexyl)-2-oxa-6-azaspiro[3.3]heptane (309); 4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-neopentylcyclohexan-1-amine (310, 325); 6-(5-(4-(azetidin-1-yl)cyclohexyl)-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (311, 335); 6-(3-isopropyl-5-(piperidin-4-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (312); 1-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a] pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-(3-methylbutan-2-yl)piperidin-4-amine (313); 1-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c] pyridin-5-yl)-N-methyl-N-(oxetan-3-yl)piperidin-4-amine (314); N-isopropyl-4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)cyclohexan-1-amine (315, 323); N-ethyl-4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-methylcyclohexan-1-amine (316, 331); N-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)cyclohexyl)tetrahydrofuran-3-amine (317, 342); 4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-isopropylcyclohexan-1-amine (318, 326); 2-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperazin-1-yl) acetamide (319); 1-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-(oxetan-3-yl)piperidin-4-amine (320); 1-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-(tetrahydro-2H-pyran-4-yl)piperidin-4-amine (321); 1-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-((3-methyloxetan-3-yl)methyl)piperidin-4-amine (322); 6-(5-(4-(azetidin-1-yl)cyclohexyl)-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (324, 332); N-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-5-yl)cyclohexyl)tetrahydrofuran-3-amine (327, 349); 2-((4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)cyclohexyl)(methyl)amino)-N-methylacetamide (328, 338); 2-((1-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidin-4-yl) amino)-N-methylacetamide (329); 2-((1-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a] pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidin-4-yl)amino)-N,N-dimethylacetamide (333); N-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-5-yl)cyclohexyl)oxetan-3-amine (334, 346); N-(2,2-difluoroethyl)-4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-5-yl)cyclohexan-1-amine (336, 350); 4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-neopentylcyclohexan-1-amine (337, 351); N-(1-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidin-4-yl)-2-(methylamino)acetamide (339); 4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a] pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-N,N-dimethylcyclohexan-1-amine (340); 6-(3-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyridine (341); 2-(dimethylamino)-1-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidin-1-yl)ethan-1-one (343); 2-(dimethylamino)-N-(1-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a] pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidin-4-yl)acetamide (344); 2-((1-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperidin-4-yl)amino)acetamide (345); 4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a] pyridin-6-yl)-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-5-yl)-N-(2-methoxyethyl) cyclohexan-1-amine (347-348); 2-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-4-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl)piperazin-1-yl)-N,N-dimethylacetamide (352); 6-(4-fluoro-3-isopropyl-5-(piperazin-1-yl)-1H-pyrrolo[2,3-c] pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (353); (R)-6-(4-fluoro-3-isopropyl-5-(2-methylpiperazin-1-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (354); 6-(4-fluoro-3-isopropyl-5-(2,6-diazaspiro[3.3]heptan-2-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (355); 2-(6-(4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-2,6-diazaspiro[3.3]heptan-2-yl)-N-methylacetamide (356); 6-(4-fluoro-3-isopropyl-5-(6-(2-(methylsulfonyl)ethyl)-2,6-diazaspiro[3.3]heptan-2-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (357); 2-(4-(4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperazin-1-yl) acetamide (358); 2-(4-(4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperazin-1-yl)-N-methylacetamide (359); 2-(4-(4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c] pyridin-5-yl)piperazin-1-yl)-N,N-dimethylacetamide (360); 6-(4-fluoro-3-isopropyl-5-(4-(2-methoxyethyl)piperazin-1-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (361); 6-(4-fluoro-3-isopropyl-5-(4-(2-(methylsulfonyl) ethyl)piperazin-1-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a] pyridine (362); 2-(4-(4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperazin-1-yl)-1-morpholinoethan-1-one (363); 1-(4-(4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c] pyridin-5-yl)piperazin-1-yl)-2-methylpropan-2-ol (364); 2-(4-(4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperazin-1-yl)acetonitrile (365); 6-(4-fluoro-3-isopropyl-5-(4-(2,2,2-trifluoroethyl)piperazin-1-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (366); 1-(6-(4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c] pyridin-5-yl)-2,6-diazaspiro[3.3]heptan-2-yl)-2-morpholinoethan-1-one (367); 2-(dimethylamino)-1-(4-(4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)piperazin-1-yl)ethan-1-one (368); 6-(4-fluoro-3-isopropyl-5-(6-(oxetan-3-yl)-2,6-diazaspiro[3.3]heptan-2-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (369); 6-(4-fluoro-3-isopropyl-5-(6-(tetrahydro-2H-pyran-4-yl)-2,6-diazaspiro[3.3]heptan-2-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (370); 6-(4-fluoro-3-isopropyl-5-(6-((tetrahydro-2H-pyran-4-yl)methyl)-2,6-diazaspiro[3.3]heptan-2-yl)-1H-pyrrolo[2,3-c] pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (371); 6-(4-fluoro-5-(6-isobutyl-2,6-diazaspiro[3.3]heptan-2-yl)-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (372); 6-(4-fluoro-3-isopropyl-5-(6-isopropyl-2,6-diazaspiro[3.3]heptan-2-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (373); 6-(5-(6-(cyclopropylmethyl)-2,6-diazaspiro[3.3]heptan-2-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (374); 6-(5-(6-(cyclobutylmethyl)-2,6-diazaspiro[3.3]heptan-2-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (375); 6-(4-fluoro-3-isopropyl-5-(6-((3-methyloxetan-3-yl)methyl)-2,6-diazaspiro[3.3]heptan-2-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (376); 6-(4-fluoro-3-isopropyl-5-(6-(1-isopropylpiperidin-4-yl)-2,6-diazaspiro[3.3]heptan-2-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (377); 6-(4-fluoro-3-isopropyl-5-(6-methyl-2,6-diazaspiro[3.3]heptan-2-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (378); 6-(5-(6-ethyl-2,6-diazaspiro[3.3]heptan-2-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a] pyridine (379); 6-(4-fluoro-3-isopropyl-5-(6-propyl-2,6-diazaspiro[3.3]heptan-2-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (380); 6-(5-(6-cyclobutyl-2,6-diazaspiro[3.3]heptan-2-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c] pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (381); 6-(4-fluoro-3-isopropyl-5-(4-(oxetan-3-yl)piperazin-1-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (382); 6-(4-fluoro-3-isopropyl-5-(4-((tetrahydro-2H-pyran-4-yl)methyl)piperazin-1-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (383); 6-(4-fluoro-3-isopropyl-5-(4-isopropylpiperazin-1-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (384); 6-(4-fluoro-3-isopropyl-5-(4-((3-methyloxetan-3-yl)methyl)piperazin-1-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (385); 6-(4-fluoro-3-isopropyl-5-(4-(tetrahydro-2H-pyran-3-yl)piperazin-1-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (386-387); 6-(4-fluoro-3-isopropyl-5-(4-(1-isopropylpiperidin-4-yl)piperazin-1-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (388); 6-(5-(4-ethylpiperazin-1-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (389); 6-(5-(4-(cyclopropylmethyl)piperazin-1-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (390); 6-(5-(4-cyclobutylpiperazin-1-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a] pyridine (391); 6-(4-fluoro-3-isopropyl-5-(2,6-diazaspiro[3.3]heptan-2-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (392); 6-(4-fluoro-3-isopropyl-5-(piperazin-1-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (393); ^®-6-(4-fluoro-3-isopropyl-5-(2-methylpiperazin-1-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (394); 2-(6-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-5-yl)-2,6-diazaspiro[3.3]heptan-2-yl)-N-methylacetamide (395); 6-(4-fluoro-3-isopropyl-5-(6-(2-(methylsulfonyl)ethyl)-2,6-diazaspiro[3.3]heptan-2-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (396); 2-(6-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-5-yl)-2,6-diazaspiro[3.3]heptan-2-yl)acetonitrile (397); 6-(4-fluoro-3-isopropyl-5-(4-(2-(methylsulfonyl)ethyl)piperazin-1-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (398); 1-(6-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-fluoro-3-isopropyl-1H- pyrrolo[2,3-c]pyridin-5-yl)-2,6-diazaspiro[3.3]heptan-2-yl)-2-morpholinoethan-1-one (399); 6-(4-fluoro-3-isopropyl-5-(6-(oxetan-3-yl)-2,6-diazaspiro[3.3]heptan-2-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (400); 6-(4-fluoro-3-isopropyl-5-(6-(tetrahydro-2H-pyran-4-yl)-2,6-diazaspiro[3.3]heptan-2-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (401); 6-(4-fluoro-5-(6-isobutyl-2,6-diazaspiro[3.3]heptan-2-yl)-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (402); 6-(4-fluoro-3-isopropyl-5-(6-isopropyl-2,6-diazaspiro[3.3]heptan-2-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (403); 6-(5-(6-(cyclobutylmethyl)-2,6-diazaspiro[3.3]heptan-2-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (404); 6-(4-fluoro-3-isopropyl-5-(6-((3-methyloxetan-3-yl)methyl)-2,6-diazaspiro[3.3]heptan-2-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (405); 6-(4-fluoro-3-isopropyl-5-(6-(1-isopropylpiperidin-4-yl)-2,6-diazaspiro[3.3]heptan-2-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (406); 6-(4-fluoro-3-isopropyl-5-(6-methyl-2,6-diazaspiro[3.3]heptan-2-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (407); 6-(5-(6-ethyl-2,6-diazaspiro[3.3]heptan-2-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (408); 6-(4-fluoro-3-isopropyl-5-(4-(oxetan-3-yl)piperazin-1-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (409); 6-(4-fluoro-3-isopropyl-5-(4-((3-methyloxetan-3-yl)methyl)piperazin-1-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (410); 6-(4-fluoro-3-isopropyl-5-(4-((tetrahydro-2H-pyran-4-yl)methyl)piperazin-1-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (411); 6-(4-fluoro-3-isopropyl-5-(4-isopropylpiperazin-1-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (412); 2-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-4-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl)piperazin-1-yl)-N-methylacetamide (413); 2-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-4-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl)piperazin-1-yl)acetamide (414); 6-(3-isopropyl-4-methyl-5-(4-(2-(methylsulfonyl)ethyl)piperazin-1-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (415); 1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-isopropyl-4-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl)piperazin-1-yl)-2-(dimethylamino)ethan-1-one (416); 6-(3-isopropyl-4-methyl-5-(4-(oxetan-3-yl)piperazin-1-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (417); 6-(3-isopropyl-4-methyl-5-(4-(tetrahydro-2H-pyran-4-yl)piperazin-1-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (418); 6-(3-isopropyl-4-methyl-5-(4-((tetrahydro-2H-pyran-4-yl)methyl)piperazin-1-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (419); 1-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c] pyridin-5-yl)piperidin-4-amine (420); 1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-5-yl)piperazin-1-yl)-2-morpholinoethan-1-one (421); 1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-5-yl)piperazin-1-yl)-2-(dimethylamino)ethan-1-one (422); 2-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-5-yl)piperazin-1-yl)-1-morpholinoethan-1-one (423); 6-(4-fluoro-3-isopropyl-5-(4-(2-methoxyethyl)piperazin-1-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (424); 6-(4-fluoro-3-isopropyl-5-(4-(methylsulfonyl)piperazin-1-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (425); 1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-5-yl)piperazin-1-yl)-2-methylpropan-2-ol (426); 1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-fluoro-3 -isopropyl- 1H-pyrrolo[2,3-c]pyridin-5-yl)piperazin-1-yl)ethan-1-one (427); 2-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-5-yl)piperazin-1-yl)-N,N-dimethylacetamide (428); 2-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-5-yl)piperazin-1-yl)acetamide (429); 6-(5-(4-(cyclopropylmethyl)piperazin-1-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (430); 6-(4-fluoro-3-isopropyl-5-(4-(tetrahydro-2H-pyran-4-yl)piperazin-1-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (431); 6-(4-fluoro-3-isopropyl-5-(4-neopentylpiperazin-1-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (432); 6-(5-(4-ethylpiperazin-1-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (433); 6-(4-fluoro-3-isopropyl-5-(6-(2,2,2-trifluoroethyl)-2,6-diazaspiro[3.3]heptan-2-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (434); 1-(6-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-5-yl)-2,6-diazaspiro[3.3]heptan-2-yl)-2-(dimethylamino)ethan-1-one (435); (R)-6-(5-(2,4-dimethylpiperazin-1-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (436); (R)-6-(4-fluoro-3-isopropyl-5-(2-methyl-4-propylpiperazin-1-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (437); (R)-1-(4-(4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-3-methylpiperazin-1-yl)-2-morpholinoethan-1-one (438); (R)-2-(dimethylamino)-1-(4-(4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-3-methylpiperazin-1-yl)ethan-1-one (439); (R)-6-(4-fluoro-3-isopropyl-5-(2-methyl-4-(oxetan-3-yl)piperazin-1-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (440); (R)-6-(5-(4-(cyclopropylmethyl)-2-methylpiperazin-1-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (441); (R)-6-(5-(4-(cyclopropylmethyl)-2-methylpiperazin-1-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (442); (R)-6-(4-fluoro-3-isopropyl-5-(4-isopropyl-2-methylpiperazin-1-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (443); (R)-6-(4-fluoro-3-isopropyl-5-(4-(2-methoxyethyl)-2-methylpiperazin-1-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (444); (R)-2-(4-(4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-3-methylpiperazin-1-yl)-N-methylacetamide (445); (R)-2-(4-(4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-3-methylpiperazin-1-yl)-N,N-dimethylacetamide (446); (R)-2-(4-(4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-3-methylpiperazin-1-yl)acetamide (447); (R)-2-(4-(4-fluoro-3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)-3-methylpiperazin-1-yl)-1-morpholinoethan-1-one (448); (R)-6-(4-fluoro-3-isopropyl-5-(2-methyl-4-(2,2,2-trifluoroethyl)piperazin-1-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (449); (R)-6-(4-fluoro-3-isopropyl-5-(2-methyl-4-(2-(methylsulfonyl)ethyl)piperazin-1-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (450); (R)-6-(4-fluoro-3-isopropyl-5-(4-(1-isopropylpiperidin-4-yl)-2-methylpiperazin-1-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (451); (R)-6-(4-fluoro-3-isopropyl-5-(2-methyl-4-(tetrahydro-2H-pyran-4-yl)piperazin-1-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (452); (R)-6-(4-fluoro-5-(4-isobutyl-2-methylpiperazin-1-yl)-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-2-yl)-8-methoxy-[1,2,4]triazolo[1,5-a]pyridine (453); (R)-6-(5-(2,4-dimethylpiperazin-1-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (454); (R)-6-(4-fluoro-3-isopropyl-5-(2-methyl-4-propylpiperazin-1-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (455); (R)-6-(4-fluoro-3-isopropyl-5-(2-methyl-4-(tetrahydro-2H-pyran-4-yl)piperazin-1-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (456); (R)-6-(4-fluoro-3-isopropyl-5-(2-methyl-4-(oxetan-3-yl)piperazin-1-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (457); (R)-6-(5-(4-cyclobutyl-2-methylpiperazin-1-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (458); (R)-6-(5-(4-(cyclopropylmethyl)-2-methylpiperazin-1-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (459); (R)-6-(4-fluoro-5-(4-isobutyl-2-methylpiperazin-1-yl)-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (460); (R)-6-(4-fluoro-3-isopropyl-5-(4-isopropyl-2-methylpiperazin-1-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (461); (R)-6-(4-fluoro-3-isopropyl-5-(4-(1-isopropylpiperidin-4-yl)-2-methylpiperazin-1-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (462); (R)-6-(4-fluoro-3-isopropyl-5-(2-methyl-4-(2-(methylsulfonyl)ethyl)piperazin-1-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (463); (R)-2-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-5-yl)-3-methylpiperazin-1-yl)acetamide (464); (R)-2-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-5-yl)-3-methylpiperazin-1-yl)-N-methylacetamide (465); (R)-2-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-5-yl)-3-methylpiperazin-1-yl)-N,N-dimethylacetamide (466); (R)-2-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-5-yl)-3-methylpiperazin-1-yl)acetonitrile (467); (R)-6-(4-fluoro-3-isopropyl-5-(2-methyl-4-(2,2,2-trifluoroethyl)piperazin-1-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (468); (R)-2-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-5-yl)-3-methylpiperazin-1-yl)-1-morpholinoethan-1-one (469); (R)-1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-5-yl)-3-methylpiperazin-1-yl)-2-(dimethylamino)ethan-1-one (470); (R)-1-(4-(2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-fluoro-3-isopropyl-1H-pyrrolo[2,3-c]pyridin-5-yl)-3-methylpiperazin-1-yl)-2-morpholinoethan-1-one (471); or (R)-6-(4-fluoro-3-isopropyl-5-(4-(2-methoxyethyl)-2-methylpiperazin-1-yl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (472).
5. A pharmaceutical composition comprising a compound according to any one of claims 1-4, N-oxide, stereoisomers, tautomers, solvates or a pharmaceutically-acceptable salt thereof; and a pharmaceutically acceptable carrier.
6. A compound according to any one of claims 1-4, N-oxide, stereoisomers, tautomers, solvates or a pharmaceutically-acceptable salt thereof, for use in therapy.
7. A compound according to any one of claims 1-4, N-oxide, stereoisomers, tautomers, solvates or a pharmaceutically-acceptable salt thereof, for use in treating autoimmune disease or chronic inflammatory disease.
8. The compound, N-oxide, stereoisomers, tautomers, solvates or a pharmaceutically-acceptable salt thereof for use according to claim 7, wherein said autoimmune disease or chronic inflammatory disease is selected from systemic lupus erythematosus (SLE), rheumatoid arthritis, multiple sclerosis (MS), and Sjögren's syndrome.